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Psoriasis is a prevalent immune-mediated inflammatory skin disease characterized by excessive abnormal proliferation of keratinocytes and infiltration of immune cells, which have significant impact on the life quality of individuals. Although biological agents and small molecule targeted drugs have brought significant clinical benefits to psoriasis patients, adverse reactions and high prices remains key issues in clinical medication of psoriasis, while natural product monomers possess high efficiency, low toxicity, anti-inflammatory and immunomodulatory properties, and bring new hope for the clinical treatment of psoriasis. Sappanone A (SA), a small molecule compound isolated from Caesalpinia sappan L, exhibits significant anti-inflammatory properties in various models, such as kidney inflammation and LPS-induced mice inflammation. Among these effects, the anti-inflammatory property of SA has received significant attention. In our study, we found that SA exhibited anti-proliferation and anti-inflammatory effects in HaCaT cells, and significantly alleviated imiquimod-induced psoriasis-like skin lesions via the inhibition of the excessive proliferation of keratinocytes and the infiltration of lymphocytes. Furthermore, the combinational analysis of network pharmacology and transcriptome sequencing revealed that SA exerted anti-psoriasis effects by inhibiting the matrix metalloproteinase 8 (Mmp8) expression and IL-17 pathway activation. In summary, we have first demonstrated that SA can be used as a novel anti-psoriasis drug, which may provide a novel strategy for the clinical treatment of psoriasis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Circular RNAs (circRNAs) are increasingly recognized for their important roles in various cancers, including papillary thyroid cancer (PTC). The specific mechanisms by which the circLIF receptor subunit alpha (circLIFR, hsa_circ_0072309) influences PTC progression remain largely unknown., Methods: In our study, CircLIFR, miR-429, and TIMP2 levels were assessed using reverse transcription-quantitative PCR. The roles of circLIFR and miR-429 in PTC cells were determined using Cell Counting Kit-8, colony formation, wound healing, and Transwell assays. Western blotting was utilized to examine the levels of TIMP2. The direct interaction between circLIFR, TIMP2, and miR-429 was confirmed using dual-luciferase reporter, RNA immunoprecipitation, and fluorescence in situ hybridization assays., Results: In PTC tissues and cells, a decrease in circLIFR and TIMP2 levels, accompanied by an increase in miR-429 levels, was observed. Overexpression of circLIFR or downregulation of miR-429 effectively suppressed the proliferation and migration of PTC cells. Conversely, the knockdown of circLIFR or overexpression of miR-429 had the opposite effect. Furthermore, circLIFR overexpression suppressed tumor growth in vivo. Mechanistically, circLIFR modulated TIMP2 expression by serving as a sponge for miR-429. Rescue experiments indicated that the antitumor effect of circLIFR could be reversed by miR-429., Conclusion: This study confirmed circLIFR as a novel tumor suppressor delayed PTC progression through the miR-429/TIMP2 axis. These findings suggested that circLIFR held promise as a potential therapeutic target for PTC., (© 2024. The Author(s).)

Gastric cancer (GC) is one of the most common malignant neoplasms of the digestive system, with China leading in terms of morbidity and mortality rates. Betulinic acid (BA) is a widely-occurring pentacyclic triterpenoid that has been reported to exhibit potent anti-inflammatory, antioxidant, and antitumor activities. BA can combat tumors by inducing apoptosis, regulating cell cycle, and inhibiting autophagy, but its mechanism of action in the context of GC is unclear. A preliminary study found that higher expression of vasodilator-stimulated phosphoprotein (VASP) was correlated with migration in the GC cell line. In this study, BGC-823 cells and MNK45 cells were treated with BA for investigating its effect on the proliferation and migration of cells. Moreover, the expression of VASP and upstream signal molecules were also investigated in this background. The results showed BA could inhibit the proliferation and migration the GC cells. Furthermore, NF-κB acted as a transcription factor to upregulate VASP expression. Moreover, BA could downregulate the expression of VASP at the protein and mRNA level by inhibiting NF-κB activity. In conclusion, these results suggest that BA could inhibit the expression of VASP by negatively regulating NF-κB, thereby inhibiting the proliferation and migration of the GC cells. Our study provides a theoretical basis for exploring the molecular mechanism underlying BA-induced inhibition of proliferation and migration in GC cells., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: The incidence of papillary thyroid cancer (PTC) is increasing, and traditional diagnostic methods are unsatisfactory. Therefore, identifying novel prognostic markers is very important. ciRS-7 has been found to play an important role in many cancers, but its role in PTC has not been reported. This study was performed to evaluate the biological role and mechanism of ciRS-7 in PTC. Material and Methods . The expression of ciRS-7 in PTC tissues and the matched adjacent tissues was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The PTC cell lines (TPC-1 and BCPAP) were used to evaluate the role of ciRS-7. ciRS-7-siRNA and overexpression plasmid were constructed and transfected into PTC cells. A CCK-8 assay and colony formation assay were performed to explore the effects of ciRS-7 on cell proliferation. Annexin V/PI staining and FACS detection were used to detect cell apoptosis. Wound healing assay was performed to detect cell migration. A transwell assay was conducted to explore the effects of ciRS-7 on invasion and migration. Western blotting was performed to evaluate protein expression. The luciferase reporter system was used to determine the underlying mechanism of miR-7., Result: ciRS-7 was highly expressed in PTC tissues and cell lines compared with the corresponding controls. In vitro study showed that ciRS-7 silencing suppressed proliferation, migration, and invasion of TPC-1 and BCPAP. Mechanistically, the effects of ciRS-7 on invasion and migration may be related to epithelial-mesenchymal transition (EMT). ciRS-7 silencing could attenuate effects on PTC cells induced by miR-7 knockdown. Epidermal growth factor receptor (EGFR), which was demonstrated to be a target of miR-7, decreased significantly in ciRS-7-siRNA PTC cells. Overexpression of EGFR also attenuated effects of PTC cells induced by silencing ciRS-7., Conclusion: ciRS-7 was significantly upregulated in PTC tissues, and it promoted the progression of PTC by regulating the miR-7/EGFR axis. ciRS-7 is a promising prognostic biomarker and therapeutic target in PTC., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Jun-ya Han et al.)

Mesenchymal stem cells (MSCs) play an important role in regulating angiogenesis and immune balance. The abnormal MSCs in proliferation and function were reported at maternal fetal interface in patients with pre-eclampsia (PE). Long non-coding RNA MALAT1 was known to regulate the function of trophoblast cells. However, it is not clear whether MALAT1 regulates MSCs to be related to PE. In the present study, we found that the expression of MALAT1 was significantly reduced in both umbilical cord tissues and MSCs in patients with severe PE. MALAT1 did not affect the phenotype and differentiation of MSCs. Of note, transfection with MALAT1 plasmid into MSCs drove the cell cycle into G2/M phase and inhibited cell apoptosis. The supernatants from MALAT1-overexpressed MSCs promoted the migration of MSCs, invasion of HTR-8/SVneo and tube formation of HUVEC, while si-MALAT1 had the opposite effects. Moreover, we found that MALAT1-induced VEGF mediated these effects of MALAT1 on MSCs. Furthermore, we found that MALAT1-overexpressed MSCs promoted M2 macrophage polarization and this effect was mediated by MALAT1-induced IDO expression, suggesting that MALAT1 may enhance the immunosuppressive properties of MSCs in vivo. In addition, we also investigated the factors that inhibit MALAT1 expression in PE and found that peroxide was a cause for MALAT1 downregulation. Taken together, our data demonstrate that MALAT1 is an important endogenous regulator in the proliferation, angiogenesis, and immunosuppressive properties of MSCs, suggesting it may be involved in the pathogenesis of PE. J. Cell. Biochem. 118: 2780-2791, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Carboxyl terminus of Hsc-70-interacting protein (CHIP), as U-box-type ubiquitin ligase, connects the chaperone and proteasome systems and plays a pivotal role in maintaining protein homeostasis in the cytoplasm. CHIP induces the ubiquitination and degradation of diverse oncogenic substrate proteins and therefore involves in the progression of tumorigenesis. In this study, the CHIP expression was examined in different human breast cancer cell lines and a group of breast cancer tissues. We found, for the first time, that CHIP expression was correlated with the molecular subtyping of breast cancer. CHIP was least expressed in the base-like subtype of breast cancer, which are triple-negative breast cancer (TNBC) breast cancer predominantly. Accordingly, CHIP expression was evidently decreased in the TNBC MDA-MB-231 breast cancer cell line. Enforced induction of CHIP in the MDA-MB-231 cells exerted no obvious influences on cellular growth and cell cycle. The apoptotic and proliferation cells in hCHIP cells were both reduced compared to the ctrl cells. The mRNA and protein expressions of the anti-apoptotic Bcl-2 and Bcl-xL were markedly increased in the hCHIP cells compared to that of the ctrl cells. The expression of RelA was significantly reduced in the nuclear extract in hCHIP cells compared to that in the ctrl cells. The protein expressions of IKKβ were markedly decreased in the hCHIP cells compared to the ctrl cells. The reduced cellular proliferation was largely due to the attenuated IKKβ-p65/NF-κB activity. Meanwhile, the invasion ability but not the migration ability was diminished when CHIP was overexpressed in the MDA-MB-231 cells. The activity of MMP2 but not MMP9 was significantly decreased in the hCHIP cells compared to the ctrl cells. Taken together, these observations here provide functional evidence for CHIP behaved as a tumor suppressor in the TNBC breast cancer cells. CHIP influenced diverse biological aspects of the MDA-MB-231 breast cancer cells. Importantly, CHIP expression is a useful indicator of the molecular subtyping of breast cancer. [ABSTRACT FROM AUTHOR]

Adipogenesis is an organized process of cellular differentiation by which pre-adipocytes differentiate towards mature adipocytes. miR-16–5p has been reported to be involved in cell proliferation, apoptosis, differentiation and angiogenesis. However little is known about miR-16–5p functional role in 3T3-L1 adipocyte differentiation. In this study, we found that miRNA-16–5p was significantly upregulated during 3T3-L1 preadipocytes differentiation towards mature adipocytes. Over-expression of miRNA-16–5p promoted mature adipocytes specific genes expression and fat droplet accumulation in vitro and in vivo. Meanwhile we have identified EPT1 as the target gene of miRNA-16–5p. Taken together, our data provided evidence to support that miRNA-16–5p promotes adipocyte differentiation by suppressing EPT1. • miR-16-5p was upregulated in 3T3-L1 pre-adipocytes differentiation. • Overexpression of miR-16-5p promoted 3T3-L1 differentiation while inhibition of miR-16-5p had an opposite function. • miR-16-5p regulated 3T3-L1 differentiation through regulating EPT1 expression. [ABSTRACT FROM AUTHOR]

This study aimed at investigating the effect of microRNA‐150 (miR‐150) on cell proliferation of Burkitt lymphoma and its molecular mechanism. Gene expression analysis was applied to identify target genes of miR‐150 in Burkitt lymphoma cell line ST486 based on the dataset from the Gene Expression Omnibus (GEO) datasets GSE86432. miRNA mimics, inhibitor and small interfering RNA (siRNA) were fluorescently labeled by Cy3, whereas plasmid vector was labeled by EGFP. Cells were viewed by fluorescence microscope and transfection efficiency was evaluated through fluorescent cell percentage. Quantitative real‐time polymerase chain reaction analysis (qRT‐PCR) and western blot were applied to detect the expression level of miR‐150 and LMO4. Cell proliferation, cell cycle, and apoptosis were explored by CCK‐8, flow cytometry. Targeting relationship was validated by the Luciferase reporter assay. Tumor xenograft and immunohistochemical analysis were conducted in nude mice model. In Burkitt lymphoma cells, miR‐150 expression was significantly lower than normal ones, whereas the expression of LMO4 was upregulated. miR‐150 might inhibit cell proliferation and promoted apoptosis in Burkitt lymphoma deterioration by downregulating LMO4. The results of tumor xenograft further confirmed the role of miR‐150 in Burkitt lymphoma. Targeting LMO4 is a significant mechanism by which miR‐150 suppresses cell growth and promotes apoptosis in Burkitt lymphoma cells, thus may provide a novel target for Burkitt lymphoma therapy in the future. Our study elucidated a potential regulatory method employing microRNA‐150 (miR‐150) and LMO4 to modulate cell proliferation and apoptosis of Burkitt lymphoma. Targeting LMO4 is a major mechanism by which miR‐150 exerts its tumor‐suppressive and proapoptotic function in Burkitt lymphoma cells, and thus may provide a potential novel target for future Burkitt lymphoma therapy [ABSTRACT FROM AUTHOR]

Background. Breast cancer (BC) is one of the most common malignant tumors in women around the world. Atorvastatin (ATO) was found to be associated with a decreased risk of recurrence and mortality in cancer. But the exact mechanism of its carcinostatic effects is unclear. The expression level of Ras homolog family member B (RhoB) in breast cancer cells was found to be upregulated after being treated with ATO. Thus, we conjecture that altered expression of RhoB induced by ATO may be decisive for the migration and progression of breast cancer. Methods. The effects of ATO on breast tumor cells in vivo and in vitro were detected by clone formation assay, CCK-8 assay, flow cytometry, wound healing, transwell assays, tumor xenograft model, and immunohistochemistry. Distribution of RhoB in different breast cancer tissues and its influence on prognosis were analyzed using the data from TCGA or GEO databases. The relationship between RhoB and PTEN/AKT pathway was detected by Western blotting and RT-qPCR. Results. ATO inhibits proliferation, invasion, EMT, and PTEN/AKT pathway and promotes apoptosis in breast tumor cells. In addition, ATO inhibits the volume and weight of breast tumor in tumor-bearing mice and upregulated RhoB in tumor tissues. The expression of RhoB in mRNA and protein level was upregulated in statin-treated breast cancer cells and downregulated in cancer tissues. Low expression of RhoB links with poor prognosis in patients with breast cancer (HR = 0.74[0.66–0.83], p =7e−8, log-rank test). Further research found that RhoB inhibits the proliferation, invasion, EMT, and PTEN/AKT signal pathway in breast tumor cells. Conclusions. The exact mechanism of ATO's carcinostatic effects in breast cancer is related to downregulating PTEN/AKT pathway via promoting RhoB. Our study also demonstrates the potential applicability of RhoB as a therapeutic target for breast cancer. [ABSTRACT FROM AUTHOR]

Esophageal cancer is one of the most common malignant cancers that arise from esophagus tissues. Fibroblast growth factor 2 (FGF2) has been implicated in multiple biological functions and was considered as an oncogenic factor in tumorigenesis. However, the effects of FGF2 in esophageal carcinoma are yet to be fully elucidated. To better understand the function of FGF2 in esophageal cancer, we used the esophageal cancer cell line ECA109 as a cell model and downregulated FGF2 expression using RNAi; the results showed that insufficient expression of FGF2 inhibited cells proliferation, migration, and invasion of ECA109 cells. Meanwhile, the proliferation, migration, and invasion abilities were stimulated after treatment of exogenous FGF2. In addition, a PI3K/Akt signalling pathway inhibitor (LY294002) alleviated the tumorigenic effects of FGF2. These findings implied that the oncogenic effects of FGF2 was mediated, at least in part, through the PI3K/Akt signalling pathway and FGF2 may be a potential therapeutic target to constrain the tumorigenesis of esophageal cancer. [ABSTRACT FROM AUTHOR]

Although the biological factors that contribute to the pathogenesis of chronic lymphocytic leukemia (CLL) remain widely unresolved, it has been suggested that dysregulated cell survival and proliferation are fundamental to this process. Constitutive classical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation protects CLL B-cells from cell death and plays a critical role in the acquisition of chemoresistance. RelB, representing the alternative NF-κB activity, functions specifically in lymphoid organogenesis and B-cell maturation. RelB indeed plays a tumor-supportive role and confers radiation resistance in tumors. However, the involvement of RelB in CLL has not been addressed. Here, we analyzed the NF-κB activation in 67 of CLL bone marrow (BM). Both the RelA and RelB activity were detected in CLL B-cells from BM, in spite of inevitable variability. Low RelB activity was linked to a favorable prognosis of CLL. The migration and adhesion abilities of CLL B-cells were not affected by the RelB activity. High RelB activity, together with the RelA activity, maintained basal survival of cells. The induction of RelA and RelB expression in the nucleus was responsible for better survival of CLL B-cells supported by bone marrow stromal cells. In addition, the presence of high RelB activity in CLL B-cells was correlated with sensitivity to proteasome inhibitor but not fludarabine. Taken together, we provided evidences that not only RelA but also RelB, subunits of NF-κB family, played an important role in the cellular behaviors of CLL cells from BM. The strength of RelB activity influenced the prognosis of CLL patients. Key message: [ABSTRACT FROM AUTHOR]

Arginine-Glycine-Aspartate (RGD) tripeptide can promote cell adhesion when present in the amino acid of proteins such as fibronectin. In order to demonstrate the bioactivity of an RGD-containing silk protein, a gene encoding the RGD motif-containing peptide GSGAGGRGDGGYGSGSS (–RGD–) derived from nonmulberry silk was designed and cloned, then multimerised and inserted into a commercial pGEX expression vector for recombinant expression of (–RGD–)n peptides. Herein, we focus on two glutathione-S-transferase (GST)-tagged fusion proteins, GST–(–RGD–)4 and GST–(–RGD–)8, which were expressed in Escherichia coli BL21, purified by GST affinity chromatography, and analyzed with sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry (MS). Target peptides (–RGD–)4 and (–RGD–)8 (6.03 and 11.5 kDa) were cleaved from the GST-tag by thrombin digestion, as verified with MS and SDS-PAGE. Isoelectric point analysis confirmed that target peptides were expressed and released in accordance with the original design. Target peptides self-assembled into a mainly α-helical structure, as determined by circular dichroism spectroscopy. Furthermore, (–RGD–)4 and (–RGD–)8 modified mulberry silk fibroin films were more effective for rapid cell adhesion, spreading and proliferative activity of L929 cells than some chemically synthesized RGD peptides modified and mulberry silk lacking the RGD motif. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is a leading public health issue worldwide. Although therapeutic approaches have improved drastically in the last decades, the prognosis of lung cancer patients remains suboptimal. The canonical nuclear transcription factor kappa B (NF-κB) signalling pathway is critical in the carcinogenesis of lung cancer. The non-canonical NF-κB signalling pathway (represented by RelB) has attracted increasing attention in the pathogenesis of haematological and epithelial malignancies. However, the function of RelB in non-small cell lung cancer (NSCLC) is still unclear. Recently, high expression of RelB has been detected in NSCLC tissues. We have also demonstrated that RelB expression is an independent prognostic factor in NSCLC patients. Methods: The mRNA and protein expression of RelB in NSCLC tissues were detected by qRT-PCR and IHC assay. The cell growth of SPC-A1 cells was detected in real-time using the x-Celligence system and xenograft tumour assays. The proliferation capability of cells was detected using a CFSE assay. Cell apoptosis was measured using Annexin V/PI staining, cell cycle was analyzed by the cytometry. Cell migration abilities were detected using the x-Celligence system and wound healing assays. The relative amounts of the active and inactive gelatinases MMP-2 and MMP-9 were examined using gelatin zymography experiments. Apoptosis of RelB depletion SPC-A1 cells after ionizing radiation at 8 Gy. The expression of cellular proliferation signal pathway related-proteins were examined by Western blot analysis. Results: The expression of RelB increases in NSCLC tissues. High RelB expression was significantly correlated with advanced-metastatic stage in patients with NSCLC. RelB-silencing inhibits cell growth in vitro and in vivo. We found that RelB affected cell proliferation by regulating AKT phosphorylation. RelB silencing attenuates the migration and invasion abilities of SPC-A1 cells and is likely related to the down regulation of MMP-9 activity and Integrin β-1 expression. In addition, RelB modulated radiation-induced survival of NSCLC cells predominantly by regulating Bcl-xL expression. Conclusions: Given the involvement of RelB in cell proliferation, migration, invasion, and radio-resistance, RelB functions as an oncogene in NSCLC cells. Our data here shed light on unexplored aspects of RelB in NSCLC. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of mortality worldwide, because of the lack of accurate diagnostic tools for the early stages of cancer. Thus, early diagnosis, which provides important information for a timely therapy of cancer, is of great significance for controlling the development of the disease and the proliferation of cancer cells and for improving the survival rates of patients. To achieve the goals of early diagnosis and timely therapy of cancer, DNA nanotechnology may be effective, since it has emerged as a valid technique for the fabrication of various nanoscale structures and devices. The resultant DNA-based nanoscale structures and devices show extraordinary performance in cancer diagnosis, owing to their predictable secondary structures, small sizes, and high biocompatibility and programmability. In particular, the rapid development of DNA nanotechnologies, such as molecular assembly technologies, endows DNA-based nanomaterials with more functionalization and intellectualization. Here, we summarize recent progress made in the development of DNA nanotechnology for the fabrication of functional and intelligent nanomaterials and highlight the prospects of this technology in cancer diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Introduction: HSPA12B is a newly discovered member of HSP70 family and plays a role in angiogenesis. YAP is an important effector in Hippo signaling and plays a critical role in cell proliferation and differentiation. Hypothesis: Endothelial HSPA12B cooperates with YAP to promote angiogenesis following MI. Methods: Wild type (WT, n=8) and endothelial specific HSPA12B deficient (HSPA12B-/-) mice (n=12) were subjected to MI. Cardiac function was measured by echocardiography and cardiac angiogenesis was evaluated by immunohistochemistry staining with anti-CD31 antibody on heart tissues 28 days after MI. Endothelial cell proliferation and angiogenesis were also evaluated by in vitro hypoxia model. Results: The values of EF% (36.7%±0.68) and FS% (17.1%±1.20) in HSPA12B-/- MI mice were significantly lower than that in WT MI mice (42.0%±1.55; 20.0%±1.45). Immunostaining with anti-CD31 antibody showed that there is less positive staining in HSPA12B-/- MI hearts compared with WT MI hearts, suggesting that HSPA12B is needed for angiogenesis following MI. We then performed in vitro experiments to investigate the mechanisms by which HSPA12B regulates endothelial cell proliferation and angiogenesis. Hypoxia (12 and 24 h) alone increased cell proliferation by 81.1%. Transfection of endothelial cells with adenovirus expressing HSPA12B (AdHSPA12B) further increased cell proliferation by 50.4% compared with hypoxia group. Matrigel assay showed AdHSPA12B transfection significantly promoted angiogenesis. Silence of either HSPA12B or YAP with respective siRNAs suppressed hypoxia induced endothelial cell proliferation and angiogenesis. YAP inhibition with a YAP inhibitor, VP suppressed AdHSPA12B promoted endothelial cell proliferation and angiogenesis. qPCR and Western blot showed that AdHSPA12B significantly increased VEGF and angiopoietin-1 expression which was suppressed by YAP inhibition. Silence of YAP with siRNA prevented hypoxia induced HSPA12B expression. Silence of HSPA12B inhibited hypoxia induced YAP expression and nuclear translocation. Immunoprecipitation showed that hypoxia promoted an interaction between HSPA12B with YAP. Conclusions: YAP could be a co-effector that cooperatively with HSPA12B promotes angiogenesis following myocardial infarction. [ABSTRACT FROM AUTHOR]