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Cytokinesis requires a apoptosis-linked gene 2 interacting protein X (ALIX) and a 55 kDa midbody centrosomal protein (CEP55) to activate the cell abscission in somatic cells. However, in germ cells, CEP55 forms intercellular bridges with testis-expressed gene 14 (TEX14), which blocks the cell abscission. These intercellular bridges play important roles in the synchronization of the germ cells and facilitate the coordinated passage of organelles and molecules between germ cells. If TEX14 is intentionally removed, intercellular bridges are disrupted, leading to sterility. Hence, a deeper understanding regarding the roles of TEX14 can provide significant insights into the inactivation of abscission and the inhibition of proliferation in cancer cells. Previous experimental studies have shown that the high affinity and low dissociation rate of TEX14 for CEP55 prevent ALIX from binding CEP55 and inactivate the germ cell abscission. However, detailed information about how TEX14 interacts with CEP55 to prevent the cell abscission is still lacking. To gain more specific insights into the interactions between CEP55 and TEX14 and the difference in reactivity between TEX14 and ALIX, we performed well-tempered metadynamics simulations of these protein complexes using atomistic models of CEP55, TEX14, and ALIX. We identified the major binding residues of TEX14 and ALIX with CEP55 by using 2D Gibbs free energy evaluations, the results of which are consistent with previous experimental studies. Our results may help design synthetic TEX14 mimicking peptides, which can bind CEP55 and facilitate the inactivation of abscission in abnormal cells, including cancer cells. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion Human skin is the first line of defence from environmental factors such as solar radiation and is susceptible to premature ageing, including a disruption in epidermal differentiation and homeostasis. We evaluated the impact of a Galactomyces Ferment Filtrate (GFF) on epidermal differentiation and response to oxidative stress.We used transcriptomics, both spatial and traditional, to assess the impact of GFF on epidermal biology and homeostasis in keratinocytes (primary or immortalized) and in ex vivo skin explant tissue. The effect of GFF on cell adhesion rates, cellular ATP levels and proliferation rates were quantitated. Oxidative phosphorylation and glycolytic rates were measured under normal and stress‐induced conditions.Transcriptomics from keratinocytes and ex vivo skin explants from multiple donors show GFF induces keratinocyte differentiation, skin barrier development and cell adhesion while simultaneously repressing cellular stress and inflammatory related processes. Spatial transcriptomics profiling of ex vivo skin indicated basal keratinocytes at the epidermal‐dermal junction and cornifying keratinocytes in the top layer of the epidermis as the primary cell types influenced by GFF treatment. Additionally, GFF significantly increases crosstalk between suprabasal and basal keratinocytes. To support these findings, we show that GFF can significantly increase cell adhesion and proliferation in keratinocytes. GFF also protected overall cellular bioenergetics under metabolic or oxidative stress conditions.Our findings provide novel insights into cellular differences and epidermal spatial localization in response to GFF, supporting previous findings that this filtrate has a significant impact on epidermal biology and homeostasis, particularly on spatially defined crosstalk. We propose that GFF can help maintain epidermal health by enhancing keratinocyte crosstalk and differentiation/proliferation balance as well as promoting an enhanced response to stress. [ABSTRACT FROM AUTHOR]

Glioma, a formidable form of brain cancer, poses significant challenges in terms of treatment and prognosis. Circular RNA nucleoporin 98 (circNUP98) has emerged as a potential regulator in various cancers, yet its role in glioma remains unclear. Here, we elucidate the functional role of circNUP98 in glioma cell proliferation, invasion, and migration, shedding light on its therapeutic implications. Glioma cells were subjected to si‐NUP98 transfection, followed by assessments of cell viability, proliferation, invasion, and migration. Subcellular localization of circNUP98 was determined, and its downstream targets were identified. We delineated the binding relationships between circNUP98 and microRNA (miR)‐520f‐3p, as well as between miR‐520f‐3p and ETS transcription factor ELK4 (ELK4). The expression levels of circNUP98/miR‐520f‐3p/ELK4 were quantified. Our findings demonstrated that circNUP98 was upregulated in glioma cells, and its inhibition significantly attenuated glioma cell proliferation, invasion, and migration. Mechanistically, circNUP98 functioned as a sponge for miR‐520f‐3p, thereby relieving the inhibitory effect of miR‐520f‐3p on ELK4. Moreover, inhibition of miR‐520f‐3p or overexpression of ELK4 partially rescued the suppressive effect of circNUP98 knockdown on glioma cell behaviors. In summary, our study unveils that circNUP98 promotes glioma cell progression via the miR‐520f‐3p/ELK4 axis, offering novel insights into the therapeutic targeting of circNUP98 in glioma treatment. [ABSTRACT FROM AUTHOR]

Nitrogen permease regulator-like 2 (NPRL2/TUSC4) is known to exert both tumor-suppressing and oncogenic effects in different types of cancers, suggesting that its actions are context dependent. Here, we delineated the molecular and functional effects of NPRL2 in malignantly transformed bronchial epithelial cells. To do so, we depleted NPRL2 in oncogenic HRas-transduced and malignantly transformed human bronchial epithelial (BEAS2B), Ras-AI-T2 cells. Intriguingly, depletion of NPRL2 in these cells induced activation of mTORC1 downstream signaling, inhibited autophagy, and impaired Ras-AI-T2 cell proliferation both in vitro and in vivo. These results suggest that NPRL2 is required for oncogenic HRas-induced cell transformation. Depletion of NPRL2 increased levels of the DNA damage marker γH2AX, the cell cycle inhibitors p21 and p27, and the apoptosis marker cleaved-PARP. These NPRL2-depleted cells first accumulated at G1 and G2, and later exhibited signs of mitotic catastrophe, which implied that NPRL2 depletion may be detrimental to oncogenic HRas-transformed cells. Additionally, NPRL2 depletion reduced heat shock factor 1/heat shock element- and NRF2/antioxidant response element-directed luciferase reporter activities in Ras-AI-T2 cells, indicating that NPRL2 depletion led to the suppression of two key cytoprotective processes in oncogenic HRas-transformed cells. Overall, our data suggest that oncogenic HRas-transduced and malignantly transformed cells may depend on NPRL2 for survival and proliferation, and depletion of NPRL2 also induces a stressed state in these cells. [ABSTRACT FROM AUTHOR]

Pod is an important organ for seed production in soybean. Pod size varies among soybean cultivars, but the mechanism is largely unknown. Here we reveal one of the factors for pod size regulation. We investigate pod size differences between two cultivars. The longer pod of 'Tachinagaha' is due to more cell number than in the short pod of 'Iyodaizu'. POD SIZE OF SOYBEAN 8 (GmPSS8), a member of the heat shock protein 70 (HSP70) family, is identified as a candidate gene for determining pod length in a major QTL for pod length. Expression of GmPSS8 in pods is higher in 'Tachinagaha' than 'Iyodaizu' and is highest in early pod development. The difference in expression is the result of an in/del polymorphism which includes an enhancer motif. Treatment with an HSP70 inhibitor reduces pod length and cell number in the pod. Additionally, shorter pods in Arabidopsis hsp70-1/-4 double mutant are rescued by overexpression of GmPSS8. Our results identify GmPSS8 as a target gene for pod length, which regulates cell number during early pod development through regulation of transcription in soybean. Our findings provide the mechanisms of pod development and suggest possible strategies enhancing yield potential in soybean. The pod is a crucial organ for soybean seed production. One of the HSP70 family genes is associated with pod size regulation mediated by duration of cell proliferation. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells (CSCs) are a specific subpopulation of cancer cells with the ability of self‐renewal, infinite proliferation, multidifferentiation and tumorigenicity, and play critical roles in cancer progression and treatment resistance. CSCs are tightly regulated by the tumor microenvironment, such as hypoxia; however, how hypoxia regulates CSCs in non‐small cell lung cancer (NSCLC) remains unclear. Methods: The proportion of ALDHhi cells was examined using the Aldefluor assay. Tankyrase inhibitor XAV939 and siRNA were used to inhibit β‐catenin while pcDNA3‐β‐catenin (S33Y) plasmid enhanced the expression of β‐catenin. Western blot was administered for protein detection. The mRNA expression was measured by quantitative real‐time PCR. Results: We found that hypoxia led to an increase in the proportion of ALDHhi cells in lung squamous carcinoma (LUSC) H520 cells, while causing a decrease in the ALDHhi cell proportion in lung adenocarcinoma (LUAD) A549 cells. Similarly, β‐catenin expression was upregulated in H520 cells but downregulated in A549 cells upon exposure to hypoxia. Mechanically, the proportion of ALDHhi cells in both cell lines was decreased by β‐catenin inhibitor or siRNA knockdown, whereas increased after β‐catenin overexpression. Furthermore, hypoxia treatment suppressed E‐cadherin expression in H520 cells and enhanced N‐cadherin and β‐catenin expression, while this effect was completely opposite in A549 cells. Conclusion: The hypoxia‐EMT‐β‐catenin axis functions as an important regulator for the proportion of CSCs in NSCLC and could potentially be explored as therapeutic targets in the future. [ABSTRACT FROM AUTHOR]

Background: Alterations in epigenetic factors are recognized as key contributors to the emergence of human cancer. The active and reversible alteration of N6‐methyladenosine (m6A) RNA is crucial for controlling gene activity and determining cellular destiny. Even with these insights, the triggering of KIAA1429 (also called VIRMA) and its role in lung adenocarcinoma (LUAD) is mostly unclear. As a result, the objective of this study was to elucidate how KIAA1429 contributes to cancer development in LUAD. Methods: This study utilized multiple methods for investigation, encompassing the in vitro functional examination of KIAA1429 in lung adenocarcinoma cells, transcriptome sequencing, methylation RNA immunoprecipitation sequencing (MeRIP‐seq), as well as RNA stability tests to ascertain the half‐life and stability of the target genes. Results: The results indicated that modifying the expression of KIAA1429 regulated the proliferation and metastasis of LUAD. By employing transcriptome sequencing alongside MeRIP‐seq analysis, the research pinpointed genes affected by m6A alterations triggered by KIAA1429. In a more detailed manner, it was discovered that KIAA1429 plays a regulatory role in the expression of ARHGAP30. Suppressing KIAA1429 results in reduced m6A levels in the mRNA of the target gene ARHGAP30, boosting its stability and expression, thus inhibiting tumor proliferation and metastasis. Conclusion: This study revealed the activation mechanism and pivotal function of KIAA1429 in LUAD tumor development, paving the way for molecular‐based interventions for LUAD. [ABSTRACT FROM AUTHOR]

Killer cell lectin-like receptor G1 (KLRG1) is an immune checkpoint receptor expressed predominantly in NK and T-cell subsets that downregulates the activation and proliferation of immune cells and participates in cell-mediated immune responses. Accumulating evidence has demonstrated the importance of KLRG1 as a noteworthy disease marker and therapeutic target that can influence disease onset, progression, and prognosis. Blocking KLRG1 has been shown to effectively mitigate the effects of downregulation in various mouse tumor models, including solid tumors and hematologic malignancies. However, KLRG1 inhibitors have not yet been approved for human use, and the understanding of KLRG1 expression and its mechanism of action in various diseases remains incomplete. In this review, we explore alterations in the distribution, structure, and signaling pathways of KLRG1 in immune cells and summarize its expression patterns and roles in the development and progression of autoimmune diseases, infectious diseases, and cancers. Additionally, we discuss the potential applications of KLRG1 as a tool for tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Chlorpyrifos is an endocrine disruptor pesticide that induces breast cancer cell proliferation through Estrogen receptor alpha pathway in humans. It also has toxic effects on some beneficial insects like bees, wasps, and arthropods, even low levels of CP can kill fish in water. Thus, it is important to efficiently remove this compound from wastewaters to get rid of its hazardous effects. Al2O3 supported ZnO.MoO3 composite was prepared as an efficient material for photo‐degradation of chlorpyrifos under UV irradiation and characterized by SEM‐EDX, XRD and TG techniques. The XRD analysis showed the orthorhombic structures with band gap of 2.86 eV for ZnO.MoO3/Al2O3 which was 2.96 eV for MoO3/Al2O3. The kinetics of degradation depicted that ZnO.MoO3/Al2O3 afforded a complete degradation of chlorpyrifos with half life of only 3 minutes which otherwise was 24 minutes in the presence of MoO3/Al2O3. The complete mineralization of chlorpyrifos was confirmed by GC/MS analysis, where no peaks of intermediates were recorded. The prepared material also exhibited good recyclability without any leaching of Zn and Mo metals. Thus, ZnO.MoO3/Al2O3 is an efficient and cost effective material for removal of chlorpyrifos. Its potential may also be explored for the removal of other hazardous organic pollutants. [ABSTRACT FROM AUTHOR]

The RAF (rapidly accelerated fibrosarcoma) kinases play critical roles in a variety of different cellular processes, including the advancement of the cell cycle, the proliferation of cells, the metabolism of cells, cell migration, and the differentiation of cells. RAF kinase was thus established as an important target for the management of cancer disease. RAF inhibitors have elicited remarkable responses and enhanced survival rates in patients with BRAF‐V600E/K melanoma, but their efficacy is restricted by resistance as a result of mutations in RAF, presenting challenges in the identification of novel RAF inhibitors. This has resulted in the development of two generations of RAF inhibitors. In the past years, a variety of heterocyclic scaffolds that are capable of inhibiting RAF activity have been discovered. Quinoline, a molecule with a fused benzene ring and N‐heterocyclic pyridine, is a prime template for designing a variety of new anticancer drugs. In the last few years, quinoline derivative has been studied for their capability to inhibit RAF kinases. In this review, we have summarized synthesis, biological study, and molecular docking studies of substituted quinoline derivatives, which have shown potent anticancer activity by inhibiting the RAF kinases. The present review would help medicinal chemists streamline and guide their efforts toward developing novel quinoline‐based RAF inhibitors, which will be beneficial for drug development. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a common malignant tumor in women, with a high mortality rate ranking first among gynecological tumors. Currently, there is insufficient understanding of the causes, pathogenesis, recurrence and metastasis of ovarian cancer, and early diagnosis and treatment still face great challenges. The sensitivity and specificity of existing ovarian cancer screening methods are still unsatisfactory. Centromere protein O (CENP-O) is a recently discovered structural centromere protein that is involved in cell death and is essential for spindle assembly, chromosome separation, and checkpoint signaling during mitosis. The abnormal high expression of CENP-O was detected in various tumors such as bladder cancer and gastric cancer, and it participates in the regulation of tumor cell proliferation. In this study, we detect the expression abundance of CENP-O mRNA in different ovarian cancer cells (ES-2, A2780, Caov-3, OVCAR-3 and SK-OV-3). The biological function changes of cell proliferation and apoptosis were detected and the role of CENP-O in ovarian cancer cell proliferation and apoptosis was explored by knocking down the expression of CENP-O gene. The results showed that CENP-O gene was significantly expressed in 5 types of ovarian cancer cell lines. After knocking down the CENP-O gene, the proliferation and cloning ability of ovarian cancer cells decreased, and the apoptosis increased. This study indicates that CENP-O has the potential to be a molecular therapeutic target, and downregulating the expression of CENP-O gene can break the unlimited proliferation ability of cancer cells and promote their apoptosis, providing a foundation and new ideas for subsequent molecular mechanism research and targeted therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Oral and maxillofacial bone tissue defects can seriously affect the physical and mental health of patients. When bone defects occur in diabetic patients, bone metabolism disorders caused by abnormal blood sugar make it more difficult to repair and treat. OBJECTIVE: To attempt to apply AOPDM1, a polypeptide with potential bioactivity to the osteogenic treatment of diabetic patients. METHODS: In normal or high-glucose environment, different concentrations of AOPDM1 were used to interfere with mouse bone marrow mesenchymal stem cells, and cell proliferation, alkaline phosphatase activity, mineralization nodules formation and osteogenic differentiation gene expression were detected. The polycaprolactone scaffold was prepared by electrospinning technology, and the scaffold was modified by polydopamine to prepare the polycaprolactonepolydopamine composite scaffold. Finally, the scaffolds were placed in AOPDM1 solution to prepare polycaprolactone-polydopamine-AOPDM1 scaffolds. The water contact angle and mechanical properties of the scaffolds were tested in the three groups. In normal or high-glucose environment, the three groups of scaffolds were co-cultured with mouse bone marrow mesenchymal stem cells, respectively, and cell adhesion, alkaline phosphatase activity and osteopontin expression were detected. RESULTS AND CONCLUSION: (1) Compared with normal environment, high-glucose environment inhibited the proliferation of bone marrow mesenchymal stem cells. In the same environment, AOPDM1 could promote the proliferation of mouse bone marrow mesenchymal stem cells. When AOPDM1 concentration was the same, alkaline phosphatase activity, mineralization ability and mRNA expression of type I collagen, osteopontin, alkaline phosphatase, and Runx2 of bone marrow mesenchymal stem cells were decreased in high-glucose environment compared with normal environment. Under the same environment, AOPDM1 could improve the alkaline phosphatase activity, mineralization ability, and mRNA expression of type I collagen, osteopontin, alkaline phosphatase and Runx2 of bone marrow mesenchymal stem cells. (2) The hydrophilicity of polycaprolactone-polydopamine scaffold and polycaprolactone-polydopamineAOPDM1 scaffold was higher than that of polycaprolactone scaffold (P < 0.001), and there was no significant difference in tensile strength and elastic modulus among the three groups (P > 0.05). Compared with the other two groups of scaffolds, the cells on the polycaprolactone-polydopamine-AOPDM1 scaffold had better adhesion morphology. When the scaffolds were identical, compared with normal environment, high-glucose environment inhibited alkaline phosphatase activity and osteopontin expression of bone marrow mesenchymal stem cells. When the environment was the same, the alkaline phosphatase activity and osteopontin expression of bone marrow mesenchymal stem cells on the polycaprolactone-polydopamine-AOPDM1 scaffold were higher than those on the other two scaffolds. (3) The above results prove that polycaprolactone-polydopamine-AOPDM composite scaffold can promote the osteogenic properties of bone marrow mesenchymal stem cells in high-glucose environment. [ABSTRACT FROM AUTHOR]

For the construction of accurate 3D tissue models in vitro, the 3D coculture model formed by spatio‐controlled distribution of multiple cells is essential. Despite the benefits of porous microspheres with low density, large surface area, and high permeability, exact spatio‐controlled distribution fails to appear in 3D coculture models by using porous microspheres as carriers. Herein, a facile method is proposed to construct a 3D coculture model with heterogeneous cell spatio‐tailored distribution using GelMA microspheres with customizable porosity structure and size based on droplet microfluidics in combination with placeholders. ATPS emulsions, containing two biocompatible immiscible aqueous phases of cell/Alg /dextran (Dex) mixture and polyethylene glycol (PEG) solution, are used as the templates to generate the placeholders. The micron‐sized porous GelMA microspheres are prepared by UV crosslinking of droplets prepared in microfluidic devices, followed by chelation of the placeholders. As a proof of concept, the 3D coculture hepatocellular carcinoma (HCC) model with HepG2 encapsulated outside the pores and HUVEC inside the pores is established. Noteworthy, the cells in the 3D coculture HCC model exhibit greater cell activity and proliferation, enhanced functionalities, and drug resistance than the control group. In conclusion, this straightforward method provides a novel approach for constructing 3D coculture models in vitro. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion The incidence of oral squamous cell carcinoma (OSCC) is increasing, and more effective treatment protocols must rapidly be developed to prevent the death of patients and ensure favorable outcomes. CircRNAs are a unique class of noncoding ribonucleic acid (RNA) molecules unaffected by RNA exonucleases. CircRNAs have more stable expression than linear RNAs and are not readily degraded; therefore, they are the newest focus of RNA research. Here, we analyze the mechanism of hsa_circ_0004771 (circ_0004771) in OSCC to provide a clinical reference.Circ_0004771 expression was measured in peripheral blood, cancerous tissues and adjacent tissues of OSCC patients. Patients were followed up for 3 years. The diagnostic value of circ_0004771 for OSCC occurrence, prognosis, recurrence and survival was analyzed with receiver operating characteristic (ROC) curves. OSCC cells were lentivirally transduced with a circ_0004771‐silencing or an empty vector to evaluate alterations in cell growth, invasion, and apoptosis. Apoptosis‐related and epithelial–mesenchymal transition (EMT)‐related protein expression was quantified. BALB/c nude mice were used for tumorigenesis experiments to evaluate tumor growth in vivo after silencing circ_0004771.Circ_0004771 expression was higher in peripheral blood and cancerous tissue of OSCC patients than in control peripheral blood and paracancerous tissue, respectively, exhibiting excellent predictive value for OSCC occurrence, prognosis, recurrence and survival. Silencing circ_0004771 decreased the growth, invasiveness, and EMT capacity and increased the apoptosis of OCC cells. In mice implanted with OSCC cells transduced with the circ_0004771‐silencing lentiviral vector, the tumor growth capacity was obviously decreased.Silencing circ_0004771 inhibits the malignant growth of OSCC. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of Fusobacterium nucleatum and microRNA-497(miR-497) on the proliferation, invasion and migration of colorectal cancer cells, and to analyze their regulatory relationships. Methods Colorectal cancer cell line HCT116 was transfected with miR-497 overexpression plasmid miR-497 mimic and was randomly divided into the infection index (MOI) 100 group, MOI 200 group, MOI 500 group, and MOI 1 000 group. They were co-cultured with Fusobacterium nucleatum with MOI of 100, 200, 500 and 1 000, respectively. Real-time fluorescent quantitative PCR was used to detect miR-497 in each group. The treatment concentration of the bacteria with the lowest expression of miR-497 was selected as the subsequent action concentration of Fusobacterium nucleatum. HCT116 cells were randomly divided into the control group, miR-497 over-expression group, miR-497 down-expression group, miR-497 over-expression negative control group and miR-497 down-expression negative control group, respectively. Cells in the control group were cultured without treatment. Cells in the miR-497 over-expression group, miR-497 down-expression group, over-expression negative control group, and down-expression negative control group were transfected with miR-497 mimics, miR497 inhibitor, mimic NC, and inhibitor NC, respectively, by Lipofectamine 2000. Cell proliferation ability was observed by CCK-8 assay, cell invasion ability was observed by Transwell assay, and cell migration ability was observed by Scratch healing assay. HCT116 cells were randomly divided into the control group, miR-497 over-expression group, overexpression negative control group, and over-expression + Fusobacterium nucleatum group, respectively. Cells in the control group were cultured without treatment, and cells in the miR-497 over-expression group were transfected with miR-497 mimic, while cells in the over-expression negative control group were transfected with mimic NC. After transfecting miR-497 mimic, cells in the overexpression + Fusobacterium nucleatum group were co-cultured with selected concentration of Fuso⁃ bacterium nucleatum. The cell proliferation ability was observed by CCK-8 assay, the cell invasion ability was observed by Transwell assay, and the cell migration ability was observed by Scratch healing assay. Results The miR-497 expression was as follows: MOI 100 group >MOI 200 group >MOI 500 group >MOI 1 000 group (all P<0. 05), and MOI 1 000 was selected as the subsequent action concentration of Fusobacterium nucleatum. Cell proliferation rate, the number of invasive cells and migration rate were as follows： miR-497 down-expression group > control group, overexpression negative control group, down-expression negative control group > miR-497 over-expression group (all P<0. 05). Cell proliferation rate, the number of invasive cells, and migration rate were as follows: miR-497 overexpression group < overexpression + Fusobacterium nucleatum group < control group, overexpression negative control group (all P<0. 05). Conclusion Fusobacterium nucleatum can promote the proliferation, invasion and migration of colorectal cancer cells through negative regulation of miR-497. [ABSTRACT FROM AUTHOR]

Background: Berberine (BBR), an isoquinoline alkaloid from Coptidis rhizoma, has been found to have powerful activities against various human malignancies, including breast cancer. However, the underlying antitumor mechanisms of BBR in breast cancer remain poorly understood. Methods: Breast cancer cells were cultured and treated with different doses (0, 20, 40, and 60 μM) of BBR for 48 h. Cell viability, proliferation, apoptosis, invasion, and migration were assessed using 3‐(4, 5‐dimethyl‐2‐thiazolyl)‐2, 5‐diphenyl‐2H‐tetrazolium bromide (MTT), 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays. Fibroblast growth factor 7 (FGF7), methyltransferase‐like 3 (METTL3), and insulin‐like growth factor‐2 mRNA‐binding protein 3 (IGF2BP3) mRNA levels and protein levels were measured using real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blot. Interaction between METTL3 and FGF7 m6A was assessed using methylated RNA immunoprecipitation (MeRIP)‐qPCR and RNA immunoprecipitation (RIP) assay. Binding ability between IGF2BP3 and FGF7 mRNA was analyzed using RIP assay. Results: BBR treatment hindered breast cancer cell proliferation, invasion, migration, and induced apoptosis. FGF7 expression was upregulated in breast cancer tissues, while its level was reduced in BBR‐treated tumor cells. FGF7 upregulation relieved the repression of BBR on breast cancer cell malignant behaviors. In mechanism, METTL3 stabilized FGF7 mRNA through the m6A‐IGF2BP3‐dependent mechanism and naturally improved FGF7 expression. BBR treatment inhibited breast cancer growth in vivo. Conclusion: BBR treatment blocked breast cancer cell growth and metastasis partly by regulating METTL3‐mediated m6A modification of FGF7 mRNA, providing a promising therapeutic target for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Solute carrier family 34 member 2 (SLC34A2) has been implicated in the development of various malignancies. However, the clinical significance and underlying molecular mechanisms of SLC34A2 in esophageal squamous cell carcinoma (ESCC) remain elusive. Methods: Western blotting, quantitative real‐time PCR and immunohistochemistry were utilized to evaluate the expression levels of SLC34A2 mRNA/protein in ESCC cell lines or tissues. Kaplan–Meier curves were employed for survival analysis. CCK‐8, colony formation, EdU and xenograft tumor model assays were conducted to determine the impact of SLC34A2 on ESCC cell proliferation. Cell cycle was examined using flow cytometry. RNA‐sequencing and enrichment analysis were carried out to explore the potential signaling pathways. The autophagic flux was evaluated by western blotting, mRFP‐GFP‐LC3 reporter system and transmission electron microscopy. Immunoprecipitation and mass spectrometry were utilized for identification of potential SLC34A2‐interacting proteins. Cycloheximide (CHX) chase and ubiquitination assays were conducted to test the protein stability. Results: The expression of SLC34A2 was significantly upregulated in ESCC and correlated with unfavorable clinicopathologic characteristics particularly the Ki‐67 labeling index and poor prognosis of ESCC patients. Overexpression of SLC34A2 promoted ESCC cell proliferation, while silencing SLC34A2 had the opposite effect. Moreover, SLC34A2 induced autophagy to promote ESCC cell proliferation, whereas inhibition of autophagy suppressed the proliferation of ESCC cells. Further studies showed that SLC34A2 interacted with an autophagy‐related protein STX17 to promote autophagy and proliferation of ESCC cells by inhibiting the ubiquitination and degradation of STX17. Conclusions: These findings indicate that SLC34A2 may serve as a prognostic biomarker for ESCC. [ABSTRACT FROM AUTHOR]

Within the intricate tapestry of molecular research, noncoding RNAs (ncRNAs) were historically overshadowed by a pervasive presumption of their inability to encode proteins or peptides. However, groundbreaking revelations have challenged this notion, unveiling select ncRNAs that surprisingly encode peptides specifically those nearing a succinct 100 amino acids. At the forefront of this epiphany stand lncRNAs and circRNAs, distinctively characterized by their embedded small open reading frames (sORFs). Increasing evidence has revealed different functions and mechanisms of peptides/proteins encoded by ncRNAs in cancer, including promotion or inhibition of cancer cell proliferation, cellular metabolism (glucose metabolism and lipid metabolism), and promotion or concerted metastasis of cancer cells. The discoveries not only accentuate the depth of ncRNA functionality but also open novel avenues for oncological research and therapeutic innovations. The main difficulties in the study of these ncRNA-derived peptides hinge crucially on precise peptide detection and sORFs identification. Here, we illuminate cutting-edge methodologies, essential instrumentation, and dedicated databases tailored for unearthing sORFs and peptides. In addition, we also conclude the potential of clinical applications in cancer therapy. [ABSTRACT FROM AUTHOR]

Summary Tree peony (Paeonia suffruticosa) undergoes bud endodormancy, and gibberellin (GA) pathway plays a crucial role in dormancy regulation. Recently, a key DELLA protein PsRGL1 has been identified as a negative regulator of bud dormancy release. However, the mechanism of GA signal to break bud dormancy remains unknown. In this study, yeast two‐hybrid screened PsSOC1 interacting with PsRGL1 through its MADS domain, and interaction was identified using pull‐down and luciferase complementation imaging assays Transformation in tree peony and hybrid poplar confirmed that PsSOC1 facilitated bud dormancy release. Transcriptome analysis of PsSOC1‐overexpressed buds indicated PsCYCD3.3 and PsEBB3 were its potential downstream targets combining with promoter survey, and they also accelerated bud dormancy release verified by genetic analysis. Yeast one‐hybrid, electrophoretic mobility shifts assays, chromatin immunoprecipitation quantitative PCR, and dual luciferase assays confirmed that PsSOC1 could directly bind to the CArG motif of PsCYCD3.3 and PsEBB3 promoters via its MADS domain. PsRGL1–PsSOC1 interaction inhibited the DNA‐binding activity of PsSOC1. Additionally, PsCYCD3.3 promoted bud dormancy release by rebooting cell proliferation. These findings elucidated a novel GA pathway, GA‐PsRGL1‐PsSOC1‐PsCYCDs, which expanded our understanding of the GA pathway in bud dormancy release. [ABSTRACT FROM AUTHOR]

An alternative and efficient route has been derived to generate the high valent [Mn(V)=O(m‐Cl‐salicylate)]+ intermediates with a series of non‐heme neutral ligand frameworks at 20 °C. The current method provides an advantage with feasibility in maintaining stoichiometric oxidant ratios along with the crucial variations of the salicylate moieties in tuning the reactivity of Mn(V)=O species. An in‐depth analysis of the Hammett studies revealed that the bound 5‐X‐salicylate (X=Cl, and NO2) drastically alters the corresponding Mn(V)=O's reactivity rates. In contrast, variations in the parent ligand frameworks resulted in consistent ρ values with increased lifetimes depicting the ligand's role in stabilization. Lastly, the complexes have been characterized to promote oxidative stress and prevent the proliferation of cancer cells effectively. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMethodsResultsConclusionsNeural stem/progenitor cells derived from olfactory neuroepithelium (hereafter olfactory neural stem/progenitor cells, ONSPCs) are emerging as a potential tool in the exploration of psychiatric disorders. The present study intended to assess whether ONSPCs could help discern individuals with schizophrenia (SZ) from non-schizophrenic (NS) subjects by exploring specific cellular and molecular features.ONSPCs were collected from 19 in-patients diagnosed with SZ and 31 NS individuals and propagated in basal medium. Mitochondrial ATP production, expression of β-catenin and cell proliferation, which are described to be altered in SZ, were examined in freshly isolated or newly thawed ONSPCs after a few culture passages.SZ-ONSPCs exhibited a lower mitochondrial ATP production and insensitivity to agents capable of positively or negatively affecting β-catenin expression with respect to NS-ONSPCs. As to proliferation, it declined in SZ-ONSPCs as the number of culture passages increased compared to a steady level of growth shown by NS-ONSPCs.The ease and safety of sample collection as well as the differences observed between NS- and SZ-ONSPCs, may lay the groundwork for a new approach to obtain biological material from a large number of living individuals and gain a better understanding of the mechanisms underlying SZ pathophysiology. [ABSTRACT FROM AUTHOR]

Glioblastoma, the most aggressive form of brain cancer, poses a significant global health challenge with a considerable mortality rate. With the predicted increase in glioblastoma incidence, there is an urgent need for more effective treatment strategies. In this study, we explore the potential of caerin 1.1 and 1.9, host defence peptides derived from an Australian tree frog, in inhibiting glioblastoma U87 and U118 cell growth. Our findings demonstrate the inhibitory impact of caerin 1.1 and 1.9 on cell growth through CCK8 assays. Additionally, these peptides effectively curtail the migration of glioblastoma cells in a cell scratch assay, exhibiting varying inhibitory effects among different cell lines. Notably, the peptides hinder the G0/S phase replication in both U87 and U118 cells, pointing to their impact on the cell cycle. Furthermore, caerin 1.1 and 1.9 show the ability to enter the cytoplasm of glioblastoma cells, influencing the morphology of mitochondria. Proteomics experiments reveal intriguing insights, with a decrease in CHI3L1 expression and an increase in PZP and JUNB expression after peptide treatment. These proteins play roles in cell energy metabolism and inflammatory response, suggesting a multifaceted impact on glioblastoma cells. In conclusion, our study underscores the substantial anticancer potential of caerin 1.1 and 1.9 against glioblastoma cells. These findings propose the peptides as promising candidates for further exploration in the realm of glioblastoma management, offering new avenues for developing effective treatment strategies. [ABSTRACT FROM AUTHOR]

There are hundreds of genes typically overexpressed in breast cancer cells and it's often assumed that their overexpression contributes to cancer progression. However, the precise proportion of these overexpressed genes contributing to tumorigenicity remains unclear. To address this gap, we undertook a comprehensive screening of a diverse set of seventy-two genes overexpressed in breast cancer. This systematic screening evaluated their potential for inducing malignant transformation and, concurrently, assessed their impact on breast cancer cell proliferation and viability. Select genes including ALDH3B1, CEACAM5, IL8, PYGO2, and WWTR1, exhibited pronounced activity in promoting tumor formation and establishing gene dependencies critical for tumorigenicity. Subsequent investigations revealed that CEACAM5 overexpression triggered the activation of signaling pathways involving β-catenin, Cdk4, and mTOR. Additionally, it conferred a growth advantage independent of exogenous insulin in defined medium and facilitated spheroid expansion by inducing multiple layers of epithelial cells while preserving a hollow lumen. Furthermore, the silencing of CEACAM5 expression synergized with tamoxifen-induced growth inhibition in breast cancer cells. These findings underscore the potential of screening overexpressed genes for both oncogenic drivers and tumor dependencies to expand the repertoire of therapeutic targets for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Airway remodelling in lung diseases can be treated by inhibiting excessive smooth muscle cell proliferation. Zedoarondiol (Zed) is a natural compound isolated from the Chinese herb Curcuma longa. The caveolin-1 (CAV-1) is widely expressed in lung cells and plays a key role in platelet-derived growth factor (PDGF) signalling and cell proliferation. This study aims to investigate the effect of Zed on human bronchial smooth muscle cell (HBSMC) proliferation and explore its potential molecular mechanisms. We assessed the effect of Zed on the proliferation of PDGF-stimulated HBSMCs and performed proteomic analysis to identify potential molecular targets and pathways. CAV1 siRNA was used to validate our findings in vitro. In PDGF-stimulated HBSMCs, Zed significantly inhibited excessive proliferation of HBSMCs. Proteomic analysis of zedoarondiol-treated HBSMCs revealed significant enrichment of differentially expressed proteins in cell proliferation-related pathways and biological processes. Zed inhibition of HBSMC proliferation was associated with upregulation of CAV1, regulation of the CAV-1/PDGF pathway and inhibition of MAPK and PI3K/AKT signalling pathway activation. Treatment of HBSMCs with CAV1 siRNA partly reversed the inhibitory effect of Zed on HBSMC proliferation. Thus, this study reveals that zedoarondiol potently inhibits HBSMC proliferation by upregulating CAV-1 expression, highlighting its potential value in airway remodelling and related diseases. [ABSTRACT FROM AUTHOR]

LHPP has been shown to be a new tumor suppressor, and has a tendency to be under-expressed in a variety of cancers. Oncolytic virotheray is a promising therapeutics for lung cancer in recent decade years. Here we successfully constructed a new recombinant oncolytic adenovirus GD55-LHPP and investigated the effect of GD55-LHPP on the growth of lung cancer cells in vitro and in vivo. The results showed that LHPP had lower expression in either lung cancer cells or clinical lung cancer tissues compared with normal cells or tissues, and GD55-LHPP effectively mediated LHPP expression in lung cancer cells. GD55-LHPP could effectively inhibit the proliferation of lung cancer cell lines and rarely affected normal cell growth. Mechanically, the oncolytic adenovirus GD55-LHPP was able to induce stronger apoptosis of lung cancer cells compared with GD55 through the activation of caspase signal pathway. Notably, GD55-LHPP also activated autophagy-related signal pathway. Further, GD55-LHPP efficiently inhibited tumor growth in lung cancer xenograft in mice and prolonged animal survival rate compared with the control GD55 or PBS. In conclusion, the novel construct GD55-LHPP provides a valuable strategy for lung cancer-targeted therapy and develop the role of tumor suppress gene LHPP in lung cancer gene therapy. [ABSTRACT FROM AUTHOR]

The atypical cadherins Fat and Dachsous (Ds) signal through the Hippo pathway to regulate growth of numerous organs, including the Drosophila wing. Here, we find that Ds-Fat signaling tunes a unique feature of cell proliferation found to control the rate of wing growth during the third instar larval phase. The duration of the cell cycle increases in direct proportion to the size of the wing, leading to linear-like growth during the third instar. Ds-Fat signaling enhances the rate at which the cell cycle lengthens with wing size, thus diminishing the rate of wing growth. We show that this results in a complex but stereotyped relative scaling of wing growth with body growth in Drosophila. Finally, we examine the dynamics of Fat and Ds protein distribution in the wing, observing graded distributions that change during growth. However, the significance of these dynamics is unclear since perturbations in expression have negligible impact on wing growth. [ABSTRACT FROM AUTHOR]

Cerium (Ce) ions exhibit multifunctional biological properties, such as anti-inflammatory, antioxidant, antimicrobial, and anticancer properties. Consequently, the development of Ce-containing biomaterials with therapeutic characteristics has received considerable research attention. In this study, Ce-doped 13–93 bioactive glass (Ce-BG) was prepared using the conventional melt-quenching method. The physical phases, surface morphologies, elemental contents, and elemental valence states of the samples were analysed. The concentration of the ions released from the samples in deionised water was determined, and their ability to induce hydroxyapatite was evaluated. The photothermal properties were tested by irradiating the samples with an 808 nm laser. The results indicate that an increase in the Ce content within a certain range did not affect the amorphous structure and morphology of the bioactive glass. Ce content variation affected the photothermal effect of Ce-BG. The wet state powder sample could be rapidly heated up to 58.24 °C under 2 W/cm2 laser irradiation at 5 mol% Ce doping, showing the best photothermal performance. Further, bacterial experiments demonstrated the good antimicrobial effect of this sample. Simulated body fluid immersion experiments revealed the ability of the Ce-BG to induce hydroxyapatite production. Furthermore, in vitro cell culture studies showed that the Ce-BG was not toxic to MC3T3-E1 cells and induced cell proliferation after 3 days. Therefore, Ce-BG is a promising bioactive material because of its favourable photothermal effects, antimicrobial properties, and biocompatibility. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a type of non-coding RNA (ncRNA) that possesses a unique single-stranded circular structure. They are primarily formed through alternative splicing of pre-mRNA (messenger RNA). The primary biological function of circRNAs is to regulate gene expression at both the transcriptional and post-transcriptional levels. Recent studies have increasingly demonstrated a close association between the dysregulation of circRNAs and the progression of diverse cancers, where they can function as either tumor suppressors or oncogenes. circWHSC1 (circNSD2) is a circular ncRNA that originates from the first 2 exons of the Wolf-Hirschhorn syndrome candidate gene (WHSC1). As Chen 2019 discovery that circWHSC1 (circNSD2) functions as a sponge for miRNAs and promotes cancer, this circRNA has garnered significant interest among researchers. circWHSC1 (circNSD2) has been found to be up-regulated in various malignant tumors, including nasopharyngeal carcinoma, lung cancer, breast cancer, liver cancer, colorectal cancer, ovarian cancer, cervical cancer, and endometrial cancer. It exerts its effects on cancer by either inhibiting or promoting the expression of related genes through direct or indirect pathways, ultimately affecting cancer proliferation, invasion, and prognosis. This article provides a comprehensive review and discussion of the biological roles of circWHSC1 (circNSD2) and its target genes in various cancers, as well as the latest research progress on related molecular biological regulatory mechanisms. Furthermore, the potential significance of circWHSC1 (circNSD2) in future clinical applications and transformations is thoroughly analyzed and discussed. [ABSTRACT FROM AUTHOR]

Aim: The most common type of cancer that leads to death worldwide is lung cancer. Despite significant surgery and chemotherapy improvements, lung cancer patient's survival rate is still poor. The RNA polymerase I subunit D (POLR1D) gene can induce various cancers. A current study reported that POLR1D plays a vital role in cancer prognosis. However, its biological function in the development of lung cancer remains unclear. Methods: Reverse transcription PCR (RT-PCR) measured the relative POLR1D protein expression level in lung cancer cell lines. Lung cancer cell proliferation, migration, and invasion were analyzed by performing cell counting kit-8 (CCK-8), and transwell. The phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/AKT) signaling pathway-related protein expressions were examined by Western blotting assay. Results: POLR1D protein expression was elevated in lung cancer. Lung cancer cell loss-of-function tests showed that POLR1D silencing could attenuate cell viability both in SK-MES-1 and in H2170 cells. Furthermore, silencing POLR1D inhibited SK-MES-1 and H2170 cells proliferation, migration, and invasion. Moreover, SK-MES-1 and H2170 cells' migration and invasion capacity were potentially suppressed by the knockdown of POLR1D. The progression of multiple cancers has been implicated in the PI3K/AKT pathway. Here, we observed that POLR1D silencing suppressed lung cancer progression by inhibition of the PI3K-Akt pathway. Conclusions: The study speculated that POLR1D might provide a new potential therapeutic possibility for treating lung cancer patients via targeting PI3K/AKT. [ABSTRACT FROM AUTHOR]

Objective To explore the effects of curcumin on the in vitro proliferation and apoptosis of mouse liver cancer Hepa1-6 cells. Methods Hepa1-6 cells in the logarithmic growth phase were divided into the control group, 10 µmol/L group, 20 µmol/L group and 40 µmol/L group, respectively, which were treated with 0, 10, 20, and 40 µmol/L of curcumin. Cell proliferation was assessed by the MTT assay, and apoptosis level was detected by FACS. Real-time quantitative PCR (RT-qPCR) was employed to detect the levels of apoptosis-related molecules Bcl-2, Caspase-3, Toll-like receptor 2 (TLR2), IFN-α, and IFN-β in Hepa1-6 cells. The secretion levels of IFN-α and IFN-β in the cell culture supernatant were determined using ELISA. Hepa1-6 cells were incubated with CD4+ T cells, CD8+ T cells and NK cells in the control group and 40 µmol/L curcumin group, respectively. FACS was used to detect the expression levels of CD69 in CD4+ T cells, CD8+ T cells and NK cells. Results The proliferation inhibition rates of Hepa1-6 cells in the 10, 20 and 40 µmol/L groups increased in a dose-dependent manner, and the inhibition rates were (36. 45 ± 2. 11) %, （46. 40 ± 2. 08) % and (82. 16 ± 3. 32) %, respectively. There was statistically significant difference in comparison with that of the control group (P<0. 05) . The apoptotic proportions of Hepa1-6 cells in the 10 µmol/L, 20 µmol/L and 40 µmol/L groups were 10. 47%, 26. 66% and 49. 81%, respectively. And the difference was statistically significant in comparison with that of the control group (P<0. 01) . RT-qPCR results showed that the transcription levels of anti-apoptotic gene Bcl-2 in the 10 µmol/L, 20 µmol/L and 40 µmol/L groups were (0. 77 ± 0. 06) times, （0. 44 ± 0. 06) times and (0. 25 ± 0. 08) times that of the control group, respectively, with statistically significant difference (all P<0. 01) . At the same time, the expression of proapoptotic gene Caspase-3 significantly increased, and the transcription levels of pro-apoptotic gene Caspase-3 in the 10 µmol/L, 20 µmol/L and 40 µmol/L groups was (1. 73 ± 0. 31) times, （2. 52 ± 0. 45) times and (3. 25 ± 0. 20) times that of the control group, respectively, with statistically significant difference (all P<0. 01) . With the increase of curcumin concentrations, TLR2 transcription levels increased gradually. TLR2 transcription levels in the 10 µmol/L, 20 µmol/L and 40 µmol/L groups were (3. 56 ± 0. 59) times, （4. 93 ± 0. 04) times and (6. 60 ± 0. 47) times that of the control group, respectively, with statistically significant difference (all P<0. 05) . In addition, the transcription levels of IFN-α in the 10 µmol/L, 20 µmol/L and 40 µmol/L groups significantly increased, which were (4. 21 ± 0. 22), （5. 54 ± 0. 39) and (8. 05 ± 0. 93) times that of the control group, respectively, and there were statistically significant differences among these groups (all P<0. 05) . The transcription levels of IFN-β were (3. 08 ± 0. 51), （5. 31 ± 0. 55) and (8. 35 ± 0. 59) times that of the control group, and the difference was statistically significant (all P<0. 01) . For IFN-α, compared with the control group ［（36. 26 ± 6. 12) pg/mL］, the levels of IFN-α secreted by cells in the 10 µmol/L, 20 µmol/L and 40 µmol/L groups were (57. 00 ± 8. 8), （82. 47 ± 4. 42), and (100. 37 ± 8. 99) pg/mL, respectively； the levels of IFN-α secreted by cells in the 10, 20, and 40 µmol/L groups were higher that that of the control group (all P<0. 01) . The levels of IFN-β secreted by the cells in the 10, 20, and 40µmol/L groups were (60. 67 ± 6. 81), （91. 33 ± 5. 51), and (144. 00 ± 10. 15) pg/mL, respectively, while that in the control group was (44. 67 ± 1. 15) pg/mL. The levels of IFN-β secreted by the cells in the 10, 20, and 40 µmol/L groups were higher than that in the control group (all P<0. 01) . In the control group, CD69 expression levels of CD4+ T cells, CD8+ T cells and NK cells were (24. 53 ± 1. 39) %, （23. 40 ± 2. 32) %, （32. 33 ± 3. 08) %, respectively. The CD69 expression levels of CD4+ T cells, CD8+ T cells and NK cells in the 40 µmol/L group were (39. 90 ± 3. 51) %, (31. 47 ± 3. 88) %, （50. 83 ± 4. 74) %, respectively. There were significant differences in CD69 levels of CD4+ T cells, CD8+ T cells and NK cells between control group and 40 µmol/L group (all P<0. 05) . Conclusion Curcumin promotes the secretion of type Ⅰ interferon by regulating the expression of TLR2, thus inhibits the proliferation of hepatocellular carcinoma cells, induces the apoptosis of hepatocellular carcinoma cells, as well as promotes the activation of immune cells. [ABSTRACT FROM AUTHOR]

Background: The clinical efficacy of Jinchuang Ointment, a traditional Chinese medicine (TCM), in treating chronic non-healing diabetic wounds has been demonstrated over the past decades. Both in vitro and in vivo angiogenic activities have been reported for its herbal ingredients, including dragon blood from the palm tree Daemonorops draco and catechu from Uncaria gambir Roxb. Additionally, crude extracts of dragon blood have exhibited hypoglycemic effects not only in animal studies but also in cell-based in vitro assays. Results: Our findings indicate that crude dragon blood extract promotes the differentiation of myoblasts into myotubes. Partially purified fractions of dragon blood crude extract significantly enhance the expression of muscle cell differentiation-related genes such as myoG, myoD, and myoHC. Our results also demonstrate that crude extracts of dragon blood can inhibit platelet-derived growth factor-induced PAI-1 expression in primary rat vascular smooth muscle cells, thereby favoring changes in hemostasis towards fibrinolysis. Consistent with previous reports, reduced expression of plasminogen activator inhibitor 1 (PAI-1) accelerates wound healing. However, further separation resulted in a significant loss of both activities, indicating the involvement of more than one compound in these processes. Stem cells play a crucial role in muscle injury repair. Neither dragon blood nor catechu alone stimulated the proliferation of human telomerase reverse transcriptase (hTERT)-immortalized and umbilical cord mesenchymal stem cells. Interestingly, the proliferation of both types of stem cells was observed when crude extracts of dragon blood and catechu were present together in the stem cell growth medium. Conclusions: Dragon blood from D. draco offers multifaceted therapeutic benefits for treating chronic nonhealing diabetic wounds from various perspectives. Most drugs in Western medicine consist of small molecules with defined ingredients. However, this is not the case in TCM, as the activities of dragon blood reported in this study. Surprisingly, the activities documented here align with descriptions in ancient Chinese medical texts dating back to A.D. 1625. [ABSTRACT FROM AUTHOR]

Background: While previous studies have primarily focused on Glucose transporter type 1 (GLUT1) related glucose metabolism signaling, we aim to discover if GLUT1 promotes tumor progression through a non-metabolic pathway. Methods: The RNA-seq and microarray data were comprehensively analyzed to evaluate the significance of GLUT1 expression in lung adenocarcinoma (LUAD). The cell proliferation, colony formation, invasion, and migration were used to test GLUT1 's oncogenic function. Co-immunoprecipitation and mass spectrum (MS) were used to uncover potential GLUT1 interacting proteins. RNA-seq, DIA-MS, western blot, and qRT-PCR to probe the change of gene and cell signaling pathways. Results: We found that GLUT1 is highly expressed in LUAD, and higher expression is related to poor patient survival. GLUT1 knockdown caused a decrease in cell proliferation, colony formation, migration, invasion, and induced apoptosis in LUAD cells. Mechanistically, GLUT1 directly interacted with phosphor-epidermal growth factor receptor (p-EGFR) and prevented EGFR protein degradation via ubiquitin-mediated proteolysis. The GLUT1 inhibitor WZB117 can increase the sensitivity of LUAD cells to EGFR-tyrosine kinase inhibitors (TKIs) Gefitinib. Conclusions: GLUT1 expression is higher in LUAD and plays an oncogenic role in lung cancer progression. Combining GLUT1 inhibitors and EGFR-TKIs could be a potential therapeutic option for LUAD treatment. [ABSTRACT FROM AUTHOR]

Lentiviral vectors derived from human immunodeficiency virus type I are widely used to deliver functional gene copies to mammalian cells for research and gene therapies. Post-transcriptional splicing of lentiviral vector transgene in transduced host and transfected producer cells presents barriers to widespread application of lentiviral vector-based therapies. The present study examined effects of indole derivative compound IDC16 on splicing of lentiviral vector transcripts in producer cells and corresponding yield of infectious lentiviral vectors. Indole IDC16 was shown previously to modify alternative splicing in human immunodeficiency virus type I. Human embryonic kidney 293T cells were transiently transfected by 3rd generation backbone and packaging plasmids using polyethyleneimine. Reverse transcription-quantitative polymerase chain reaction of the fraction of unspliced genomes in human embryonic kidney 293T cells increased up to 31% upon the indole's treatment at 2.5 uM. Corresponding yield of infectious lentiviral vectors decreased up to 4.5-fold in a cell transduction assay. Adjusting timing and duration of IDC16 treatment indicated that the indole's disruption of early stages of transfection and cell cycle had a greater effect on exponential time course of lentiviral vector production than its reduction of post-transcriptional splicing. Decrease in transfected human embryonic kidney 293T proliferation by IDC16 became significant at 10 uM. These findings indicated contributions by early-stage transfection, cell proliferation, and post-transcriptional splicing in transient transfection of human embryonic kidney 293T cells for lentiviral vector production. [ABSTRACT FROM AUTHOR]

The extracellular matrix (ECM) serves as a scaffold for cells and plays an essential role in regulating numerous cellular processes, including cell migration and proliferation. Due to limitations in specimen preparation for conventional roomtemperature electron microscopy, we lack structural knowledge on how ECM components are secreted, remodeled, and interact with surrounding cells. We have developed a 3D-ECM platform compatible with sample thinning by cryo-focused ion beam milling, the lift-out extraction procedure, and cryo-electron tomography. Our workflow implements cell-derived matrices (CDMs) grown on EM grids, resulting in a versatile tool closely mimicking ECM environments. This allows us to visualize ECM for the first time in its hydrated, native context. Our data reveal an intricate network of extracellular fibers, their positioning relative to matrix-secreting cells, and previously unresolved structural entities. Our workflow and results add to the structural atlas of the ECM, providing novel insights into its secretion and assembly. [ABSTRACT FROM AUTHOR]

Gut microbiota plays a crucial role in gastrointestinal tumors. Additionally, gut microbes influence the progression of esophageal cancer. However, the major bacterial genera that affect the invasion and metastasis of esophageal cancer remain unknown, and the underlying mechanisms remain unclear. Here, we investigated the gut flora and metabolites of patients with esophageal squamous cell carcinoma and found abundant Bacteroides and increased secretion and entry of the surface antigen lipopolysaccharide (LPS) into the blood, causing inflammatory changes in the body. We confirmed these results in a mouse model of 4NQO-induced esophageal carcinoma in situ and further identified epithelial–mesenchymal transition (EMT) occurrence and TLR4/Myd88/NF-κB pathway activation in mouse esophageal tumors. Additionally, in vitro experiments revealed that LPS from Bacteroides fragile promoted esophageal cancer cell proliferation, migration, and invasion, and induced EMT by activating the TLR4/Myd88/NF-κB pathway. These results reveal that Bacteroides are closely associated with esophageal cancer progression through a higher inflammatory response level and signaling pathway activation that are both common to inflammation and tumors induced by LPS, providing a new biological target for esophageal cancer prevention or treatment. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming is widely recognized as a hallmark of malignant tumors, and the targeting of metabolism has emerged as an appealing approach for cancer treatment. Mitochondria, as pivotal organelles, play a crucial role in the metabolic regulation of tumor cells, and their morphological and functional alterations are intricately linked to the biological characteristics of tumors. As a key regulatory subunit of mitochondria, mitochondrial inner membrane protein (IMMT), plays a vital role in degenerative diseases, but its role in tumor is almost unknown. The objective of this research was to investigate the roles that IMMT play in the development and progression of breast cancer (BC), as well as to elucidate the underlying biological mechanisms that drive these effects. In this study, it was confirmed that the expression of IMMT in BC tissues was significantly higher than that in normal tissues. The analysis of The Cancer Genome Atlas (TCGA) database revealed that IMMT can serve as an independent prognostic factor for BC patients. Additionally, verification in clinical specimens of BC demonstrated a positive association between high IMMT expression and larger tumor size (> 2 cm), Ki-67 expression (> 15%), and HER-2 status. Furthermore, in vitro experiments have substantiated that the suppression of IMMT expression resulted in a reduction in cell proliferation and alterations in mitochondrial cristae, concomitant with the liberation of cytochrome c, but it did not elicit mitochondrial apoptosis. Through Gene Set Enrichment Analysis (GSEA) analysis, we have predicted the associated metabolic genes and discovered that IMMT potentially modulates the advancement of BC through its interaction with 16 metabolic-related genes, and the changes in glycolysis related pathways have been validated in BC cell lines after IMMT inhibition. Consequently, this investigation furnishes compelling evidence supporting the classification of IMMT as prognostic marker in BC, and underscoring its prospective utility as a novel target for metabolic therapy. [ABSTRACT FROM AUTHOR]

Zinc finger proteins (ZNFs) play a significant role in the initiation and progression of tumors. Nevertheless, the specific contribution of ZNF610 to lung adenocarcinoma (LUAD) remains poorly understood. This study sought is to elucidate the role of ZNF610 in LUAD. Transcript data of LUAD were obtained from The Cancer Genome Atlas Program (TCGA) database and processed via R program. The expression of ZNF610 was assessed in various cell lines. To compare the proliferative capacity of cells with or without ZNF610 silencing, CCK8, cell colony formation assay, and Celigo label‐free cell counting assay were employed. Furthermore, transwell migration and invasion assays were conducted to evaluate the migratory and invasive abilities of the cells. The expression levels of genes and proteins were assessed using quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot techniques. In different LUAD cells, the expression level of ZNF610 was found to be significantly higher in LUAD cells compared to MRC‐5 and BASE‐2B cells. Moreover, the silencing of ZNF610 resulted in a decrease in cell proliferation and migration abilities. Additionally, the apoptosis rate of cells increased upon silencing ZNF610. Notably, the proportion of cells in the G0/G1 phase increased, while the proportion of cells in the S phase decreased following ZNF610 silencing. Finally, β‐catenin and snail were identified as downstream targets of ZNF610 in cells. Our findings suggest that silencing ZNF610 could inhibit LUAD cell proliferation and migration, possibly through the downregulation of β‐catenin and snail. Significance statement: Lung adenocarcinoma (LUAD) is an aggressive cancer, and elucidating novel therapeutic targets is crucial. Our study identified ZNF610 as a potential target by demonstrating its overexpression in LUAD cells and its functional role in cell proliferation, migration, and apoptosis. Silencing ZNF610 inhibited these processes and altered cell cycle distribution, suggesting its potential as a therapeutic target. Furthermore, we identified β‐catenin and snail as downstream targets of ZNF610, providing mechanistic insights into its oncogenic functions. These findings warrant further investigation of ZNF610 as a therapeutic target for LUAD. [ABSTRACT FROM AUTHOR]

A joint modeling framework was developed using data from 75 patients of early amcenestrant phase I–II AMEERA‐1‐2 dose escalation and expansion cohorts. A semi‐mechanistic tumor growth inhibition (TGI) model was developed. It accounts for the dynamics of sensitive and resistant tumor cells, an exposure‐driven effect on tumor proliferation of sensitive cells, and a delay in the initiation of treatment effect to describe the time course of target lesion tumor size (TS) data. Individual treatment exposure overtime was introduced in the model using concentrations predicted by a population pharmacokinetic model of amcenestrant. This joint modeling framework integrated complex RECISTv1.1 criteria information, linked TS metrics to progression‐free survival (PFS), and was externally evaluated using the randomized phase II trial AMEERA‐3. We demonstrated that the instantaneous rate of change in TS (TS slope) was an important predictor of PFS and the developed joint model was able to predict well the PFS of amcenestrant phase II monotherapy trial using only early phase I–II data. This provides a good modeling and simulation tool to inform early development decisions. [ABSTRACT FROM AUTHOR]

Specialized pro‐resolving lipid mediators (SPMs) are known for their anti‐inflammatory and pro‐resolving actions. The aim of the present study was to find new functions of the SPM resolvin D1n‐3 DPA (RvD1n‐3 DPA) on oral epithelial cells. As a starting point, we used a dataset obtained by RNA high‐throughput sequencing of oral epithelial cells exposed to TNF‐α and RvD1n‐3 DPA versus TNF‐α alone. GOrilla enrichment analysis showed that the actin cytoskeleton was significantly overrepresented after adjustment for multiple hypothesis testing. As actin, amongst others, is closely related to cell migration, we then explored whether RvD1n‐3 DPA can modulate oral epithelial cell migration. To this end, we used an in vitro cell migration model, including TNF‐α treatment, to mimic an inflammatory cell state. The analysis revealed that RvD1n‐3 DPA increased oral epithelial cell migration in the presence but not in the absence of TNF‐α. Addition of RvD1n‐3 DPA also induced F actin accumulation around the cell nucleus, indicating that RvD1n‐3 DPA potentially can mediate processes of intracellular transport. This indicates that this lipid mediator may be a promising therapeutic candidate in oral mucosal wound healing. [ABSTRACT FROM AUTHOR]

Objective: A series of new 7-methoxytetrahydropyrrolo[3,4-a]carbazole-1,3-diones derivatives (VIa–VIc) modified with hydroxyl-alkyl side chains have been synthesized and examined their biological activity. Based on their interaction with the DNA of the calf thymus (CT), the side chain effect on their ability to bind DNA was assessed and their cytotoxicity was assessed. Methods: The DNA-binding properties were studied by absorption spectroscopy, EB-DNA displacement, circular dichroism, viscosity, and thermal denaturation measurements. The anticancer activities of (VIa–VIc) were evaluated on different cell lines A549, HepG2, and K562. Results and Discussion: The experimental evidences indicated that compounds could interact with CT-DNA through intercalation into the base pairs of DNA. Compound (VIc) exhibited utmost DNA binding propensity and cytotoxicity compared to the compounds (VIa) and (VIb). The intrinsic binding constant values for compounds (VIa–VIc) were 1.0 × 104, 0.372 × 104, and 2.14 × 105 M–1 respectively, suggesting side chains plays a key role in DNA binding affinity. Conclusions: We talked about their structure and the relevance to bioactivity. Compound (VIc) has stronger cytotoxic action and more efficient DNA binding in similar experimental settings. [ABSTRACT FROM AUTHOR]

As a common environmental contaminant, perfluorooctane sulfonate (PFOS) can be detected in environmental media, plants, animal organs, and humans. PFOS has multiple toxic effects on neural regeneration and development in planarians, zebrafish, and other animals, but the toxic effects exerted on the maintenance of cellular homeostasis and the expression of neuron-related genes during planarian regeneration remain unclear. In this study, planarians were cut at the post-auricle level and then exposed to PFOS for different lengths of time. It was found that PFOS exposure promoted the expression of DjpiwiA, a specific marker gene of neoblasts, which was related to regeneration and the maintenance of homeostasis in planarians. High PFOS exposure inhibited the proliferation of regenerating planarian neoblasts, and there was also an effect on apoptosis in regenerating planarians after PFOS exposure. The results suggested that PFOS exposure in regenerating planarians resulted in a reduction in the density of brain ganglia and inconspicuous brain branching and altered neuronal gene expression in the nervous system. The findings of this study suggest that PFOS has multiple toxic effects on the planarian regeneration and provide a basis for uncovering the toxic effects of PFOS on stem cell proliferation, apoptosis, and the CNS. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma (OS) is a primary bone malignancy that mostly affects young people, characterized by high metastatic potential, and a marked chemoresistance that is responsible for disease relapse in most patients. Therefore, it is necessary to identify novel molecules to setup targeted strategies to improve the clinical outcome. The enzyme nicotinamide N‐methyltransferase (NNMT) catalyses the N‐methylation of nicotinamide and other analogs, playing a crucial role in the biotransformation of drugs and xenobiotics. NNMT overexpression was reported in a wide variety of cancers, and several studies demonstrated that is able to promote cell proliferation, migration and resistance to chemotherapy. The aim of this study was to explore the potential involvement of NNMT in OS. Methods: Immunohistochemical analyses have been performed to evaluate NNMT expression in selected OS and healthy bone tissue samples. Subsequently, OS cell lines have been transfected with vectors targeting NNMT mRNA (shRNAs) and the impact of this downregulation on migration, cell proliferation, and response to chemotherapeutic treatment was also analysed by wound healing, MTT, SRB and Trypan blue assays, respectively. Results: Results showed that OS samples display a significantly higher NNMT expression compared with healthy tissue. Preliminary results suggest that NNMT silencing in OS cell lines is associated to a decrease of cell proliferation and migration, as well as to enhanced sensitivity to chemotherapy. Data obtained showed that NNMT may represent an interesting marker for OS detection and a promising target for effective anti‐cancer therapy. [ABSTRACT FROM AUTHOR]

Objective SIRT1, an NAD+-dependent deacetylase, is upregulated in CD4+ T cells from SLE patients and MRL/lpr lupus-like mice. This study aimed to explore the role of SIRT1 in follicular helper T (Tfh) cell expansion and its potential value as a therapeutic target for SLE. Methods Frequencies of CD4+CXCR5+PD-1+ Tfh cells in peripheral blood from SLE patients and their expression of SIRT1 and B cell lymphoma 6 (BCL-6) were determined with flow cytometry. Naïve CD4+ T cells were transfected with SIRT1 -expressing lentivirus and small interfering RNA (siRNA) targeting SIRT1 , respectively, and then cultured under Tfh-polarizing conditions to study the impact of SIRT1 on Tfh cell differentiation. This impact was also evaluated in both CD4+ T cells and naïve CD4+ T cells by treatment with SIRT1 inhibitors (EX527 and nicotinamide) in vitro. MRL/lpr mice and pristane-induced lupus mice were treated with continuous daily intake of nicotinamide, and their lupus phenotypes (including skin rash, arthritis, proteinuria and serum anti-dsDNA autoantibodies) were compared with those of controls. Results Expression of SIRT1 was elevated in Tfh cells from SLE patients and was positively correlated with Tfh cell frequencies. SIRT1 expression gradually increased during Tfh cell differentiation. Overexpression of SIRT1 by lentiviral vectors significantly promoted Tfh cell differentiation/proliferation. Reciprocally, suppressing expression of SIRT1 by siRNA and inhibiting SIRT1 activity by EX-527 or nicotinamide hindered Tfh cell expansion. Continuous daily intake of nicotinamide alleviated lupus-like phenotypes and decreased serum CXCL13 in the two mouse models. Conclusion SIRT1 overexpression contributed to the expansion of Tfh cells in SLE and may serve as a potential target for treatment. [ABSTRACT FROM AUTHOR]

Cancer is most commonly viewed as resulting from somatic mutations enhancing proliferation and invasion. Some hypotheses further propose that these new capacities reveal a breakdown of multicellularity allowing cancer cells to escape proliferation and cooperation control mechanisms that were implemented during evolution of multicellularity. Here we critically review one such hypothesis, named "atavism," which puts forward the idea that cancer results from the re‐expression of normally repressed genes forming a program, or toolbox, inherited from unicellular or simple multicellular ancestors. This hypothesis places cancer in an interesting evolutionary perspective that has not been widely explored and deserves attention. Thinking about cancer within an evolutionary framework, especially the major transitions to multicellularity, offers particularly promising perspectives. It is therefore of the utmost important to analyze why one approach that tries to achieve this aim, the atavism hypothesis, has not so far emerged as a major theory on cancer. We outline the features of the atavism hypothesis that, would benefit from clarification and, if possible, unification. [ABSTRACT FROM AUTHOR]

This study aimed to examine the expression and biological functions of ACTL6A in glioma cells (U251), the effects of sulforaphane on the growth of U251 cells and the involvement of the ACTL6A/PGK1 pathway in those effects. The U251 cell line was transfected with ACTL6A over-expression plasmids to upregulate the protein, or with ACTL6A inhibitor to underexpress it, then treated with different concentrations of sulforaphane. Cell viability, proliferation, and apoptosis were assessed using standard assays, and levels of mRNAs encoding ACTL6A, PGK1, cyclin D1, Myc, Bax or Bcl-2 were measured using quantitative real-time polymerase chain reaction (qRT-PCR). ACTL6A and PGK1 were expressed at higher levels in glioma cell lines than in normal HEB cells. ACTL6A overexpression upregulated PGK1, whereas ACTL6A inhibition had the opposite effect. ACTL6A overexpression induced proliferation, whereas its inhibition repressed proliferation, enhanced apoptosis, and halted the cell cycle. Moreover, sulforaphane suppressed the growth of U251 cells by inactivating the ACTL6A/PGK1 axis. ACTL6A acts via PGK1 to play a critical role in glioma cell survival and proliferation, and sulforaphane targets it to inhibit glioma. [ABSTRACT FROM AUTHOR]

Simple Summary: Dermal papilla cells (DPCs) play a key role in the growth and development of hair follicles, and their number can regulate the shape and size of hair. Previous studies found that the BMP7 gene is differentially expressed in Hu sheep lamb skin of different pattern types and plays a key role in the proliferation of Hu sheep DPCs. However, the molecular mechanism of the differential expression of the BMP7 gene remains unclear. Here, we aim to investigate the cause of the BMP7 gene differentially expressed in Hu sheep lamb skin of different pattern types. Our findings demonstrate that DNA methylation modification can affect the expression of the BMP7 gene and can regulate the proliferation and cell cycle of Hu sheep DPCs. Previous studies have shown that the BMP7 gene is differentially expressed in Hu sheep lamb skin of different pattern types, and its expression level is significantly correlated with hair follicle indices of different pattern types, but the molecular mechanism of the differential expression of the BMP7 gene remains unclear. This study investigated the effect of DNA methylation on the transcriptional expression of BMP7. Firstly, we found that the mRNA expression of the BMP7 gene and the activity of the core promoter of the BMP7 gene were upregulated after 5-Aza-Deoxycytidine-induced demethylation treatment using qRT-PCR and double luciferase reporter assay. Then, we found that the proliferation of Hu sheep DPCs in vitro was promoted after 5-Aza-Deoxycytidine-induced demethylation treatment through qRT-PCR, CCK-8, and EdU assay, and that the overexpression of DNMT1 in DPCs induced the opposite effect. In addition, the results of the cell cycle assay reveal that the percentage of cells in the S phase was increased after 5-Aza-Deoxycytidine-induced demethylation treatment, and that the percentage of cells in the S phase was decreased after overexpression of DNMT1 in DPCs. This study indicated that the differential expression of the BMP7 gene in different patterns of Hu sheep lamb skin may be regulated by DNA methylation modification. In addition, DNA methylation can regulate the proliferation and cell cycle of DPCs in Hu sheep. [ABSTRACT FROM AUTHOR]

Osteoblasts are mechanosensitive cells. Tensile stress with different conditions, including loading time, frequency, magnitude, etc. would cause varied responses in osteoblasts. However, it was not clarified that the effect of the loading types on the osteoblasts. In this study, we focused on the effect of varied tensile stress types on osteoblasts, including isotropic stretch, biaxial stretch, and uniaxial stretch with the negative ratio of transverse strain to axial strain (NR) −1, 0, and 0.2 respectively. Cell proliferation was determined to be most efficient when stimulated by 6% strain at a frequency of 1 Hz and a negative value of 0 for 1 h/day. The varied strain resulted in a thickening of the F-actin cytoskeleton and a thinning of the nucleus. Nuclear flattening caused Yes-associated protein (YAP) to be transported to the nucleus. It was suggested that the influence of loading types on the mechanobiology responses must be noticed. The mechanism of cell mechanical sensitivity under varied loading types was explored, which would provide good suggestions for designing microstructures to control deformation patterns in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Intestinal epithelium renewal strictly depends on fine regulation between cell proliferation, differentiation, and apoptosis. While murine intestinal microbiota has been shown to modify some epithelial cell kinetics parameters, less is known about the role of the human intestinal microbiota. Here, we investigated the rate of intestinal cell proliferation in C3H/HeN germ-free mice associated with human flora (HFA, n = 8), and in germ-free (n = 15) and holoxenic mice (n = 16). One hour before sacrifice, all mice were intraperitoneally inoculated with 5-bromodeoxyuridine (BrdU), and the number of BrdU-positive cells/total cells (labelling index, LI), both in the jejunum and the colon, was evaluated by immunohistochemistry. Samples were also observed by scanning electron microscopy (SEM). Moreover, the microbiota composition in the large bowel of the HFA mice was compared to that of of human donor's fecal sample. No differences in LI were found in the small bowels of the HFA, holoxenic, and germ-free mice. Conversely, the LI in the large bowel of the HFA mice was significantly higher than that in the germ-free and holoxenic counterparts (p = 0.017 and p = 0.048, respectively). In the holoxenic and HFA mice, the SEM analysis disclosed different types of bacteria in close contact with the intestinal epithelium. Finally, the colonic microbiota composition of the HFA mice widely overlapped with that of the human donor in terms of dominant populations, although Bifidobacteria and Lactobacilli disappeared. Despite the small sample size analyzed in this study, these preliminary findings suggest that human intestinal microbiota may promote a high proliferation rate of colonic mucosa. In light of the well-known role of uncontrolled proliferation in colorectal carcinogenesis, these results may deserve further investigation in a larger population study. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) and reactive nitrogen species (RNS) exert profound biological impacts dictated by their chemistry. Understanding their spatial distribution is essential for deciphering their roles in diverse biological processes. This review establishes a framework for the chemical biology of NO and RNS, exploring their dynamic reactions within the context of cancer. Concentration-dependent signaling reveals distinctive processes in cancer, with three levels of NO influencing oncogenic properties. In this context, NO plays a crucial role in cancer cell proliferation, metastasis, chemotherapy resistance, and immune suppression. Increased NOS2 expression correlates with poor survival across different tumors, including breast cancer. Additionally, NOS2 can crosstalk with the proinflammatory enzyme cyclooxygenase-2 (COX-2) to promote cancer progression. NOS2 and COX-2 co-expression establishes a positive feed-forward loop, driving immunosuppression and metastasis in estrogen receptor-negative (ER-) breast cancer. Spatial evaluation of NOS2 and COX-2 reveals orthogonal expression, suggesting the unique roles of these niches in the tumor microenvironment (TME). NOS2 and COX2 niche formation requires IFN-γ and cytokine-releasing cells. These niches contribute to poor clinical outcomes, emphasizing their role in cancer progression. Strategies to target these markers include direct inhibition, involving pan-inhibitors and selective inhibitors, as well as indirect approaches targeting their induction or downstream effectors. Compounds from cruciferous vegetables are potential candidates for NOS2 and COX-2 inhibition offering therapeutic applications. Thus, understanding the chemical biology of NO and RNS, their spatial distribution, and their implications in cancer progression provides valuable insights for developing targeted therapies and preventive strategies. [ABSTRACT FROM AUTHOR]

Hypopharyngeal squamous cell carcinoma (HSCC) is a kind of malignant tumor with a poor prognosis and low quality of life in the otolaryngology department. It has been found that microRNA (miRNA) plays an important role in the occurrence and development of various tumors. This study found that the expression level of miRNA-107 (miR-107) in HSCC was significantly reduced. Subsequently, we screened out the downstream direct target gene Neuronal Vesicle Trafficking Associated 1 (NSG1) related to miR-107 through bioinformatics analysis and found that the expression of NSG1 was increased in HSCC tissues. Following the overexpression of miR-107 in HSCC cells, it was observed that miR-107 directly suppressed NSG1 expression, leading to increased apoptosis, decreased proliferation, and reduced invasion capabilities of HSCC cells. Subsequent experiments involving the overexpression and knockdown of NSG1 in HSCC cells demonstrated that elevated NSG1 levels enhanced cell proliferation, migration, and invasion, while the opposite effect was observed upon NSG1 knockdown. Further investigations revealed that changes in NSG1 levels in the HSCC cells were accompanied by alterations in ERK signaling pathway proteins, suggesting a potential regulatory role of NSG1 in HSCC cell proliferation, migration, and invasion through the ERK pathway. These findings highlight the significance of miR-107 and NSG1 in hypopharyngeal cancer metastasis, offering promising targets for therapeutic interventions and prognostic evaluations for HSCC. [ABSTRACT FROM AUTHOR]