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Circular RNAs (circRNAs) are non-coding RNAs that exist naturally in various eukaryotic organisms. The majority of circRNAs are produced through the splicing of exons, although there are a limited number that are generated through the circularization of introns. Studies have shown that circRNAs play an irreplaceable role in the pathogenesis, disease progression, diagnosis, and targeted therapy of motor system tumors (osteosarcoma), metabolic diseases (osteoporosis), and degenerative diseases (osteonecrosis of the femoral head, osteoarthritis, intervertebral disc degeneration). This review summarizes the advancements in circRNA detection techniques and the research progress of circRNAs in orthopedic diseases. [ABSTRACT FROM AUTHOR]

Background: RNA modifications, a central aspect of epitranscriptomics, add a regulatory layer to gene expression by modifying RNA function without altering nucleotide sequences. These modifications play vital roles across RNA species, influencing RNA stability, translation, and interaction dynamics, and are regulated by specific enzymes that add, remove, and interpret these chemical marks. Objective: This review examines the role of aberrant RNA modifications in cancer progression, exploring their potential as diagnostic and prognostic biomarkers and as therapeutic targets. We focus on how altered RNA modification patterns impact oncogenes, tumor suppressor genes, and overall tumor behavior. Methods: We performed an in-depth analysis of recent studies and advances in RNA modification research, highlighting key types and functions of RNA modifications and their roles in cancer biology. Studies involving preclinical models targeting RNA-modifying enzymes were reviewed to assess therapeutic efficacy and potential clinical applications. Results: Aberrant RNA modifications were found to significantly influence cancer initiation, growth, and metastasis. Dysregulation of RNA-modifying enzymes led to altered gene expression profiles in oncogenes and tumor suppressors, correlating with tumor aggressiveness, patient outcomes, and response to immunotherapy. Notably, inhibitors of these enzymes demonstrated potential in preclinical models by reducing tumor growth and enhancing the efficacy of existing cancer treatments. Conclusions: RNA modifications present promising avenues for cancer diagnosis, prognosis, and therapy. Understanding the mechanisms of RNA modification dysregulation is essential for developing targeted treatments that improve patient outcomes. Further research will deepen insights into these pathways and support the clinical translation of RNA modification-targeted therapies. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer globally, with limited effective biomarkers and sensitive therapeutic targets. An increasing number of studies have highlighted the critical role of tumor microenvironment (TME) imbalances, particularly immune escape due to impaired chemokine-mediated trafficking, in tumorigenesis and progression. Notably, CC chemokines (CCLs) have been shown to either promote or inhibit angiogenesis, metastasis, and immune responses in tumors, thereby influencing cancer development and patient outcomes. However, the diagnostic and prognostic significance of CCLs in CRC remains unclear. In this study, multiple online tools for bioinformatics analyses were utilized. The findings revealed that the mRNA expression levels of CCL3, CCL4, and CCL26 were significantly elevated in CRC tissues compared to normal tissues, whereas CCL2, CCL5, CCL11, CCL21, and CCL28 mRNA levels were markedly downregulated. Additionally, dysregulation of CCL4, CCL5, and CCL21 was strongly associated with clinical staging, and elevated levels of CCL4, CCL11, and CCL28 were linked to significantly prolonged survival in CRC patients. Functional enrichment analysis indicated that the cellular roles of CCLs were predominantly associated with the chemokine, Wnt, and Toll-like receptor signaling pathways, as well as protein kinase activity. Furthermore, transcriptional regulation of most CCLs involved RELA and NFKB1. Key downstream targets included members of the SRC family of tyrosine kinases (HCK, LYN, and LCK), serine/threonine kinases (ATR and ATM), and others such as CSNK1G2, NEK2, and CDK2. Moreover, CCLs (CCL2, CCL3, CCL4, CCL5, CCL11, CCL21, and CCL28) exhibited strong correlations with major infiltration-related immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. In conclusion, our study provides novel insights into the potential utility of CCLs as biomarkers and therapeutic targets for CRC prevention and immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Thoracotomy is a common treatment for non-small cell lung cancer (NSCLC). However, the significant trauma from this procedure can limit patients' postoperative prognosis. Therefore, it's crucial to find an easily detected indicator that can predict the prognosis of NSCLC patients undergoing thoracotomy. FAM83A-AS1 was hypothesized as a predictor for the therapeutic effectiveness of thoracotomy. We evaluated its correlation with patient outcomes and its significance in predicting postoperative prognosis, with the aim of providing a reference to improve postoperative prognosis of thoracotomy. Materials and methods: The study enrolled patients with NSCLC who underwent thoracotomy, and tissue samples were collected during surgery. Blood samples were collected preoperatively and three days postoperatively. PCR was used to analyze plasma FAM83A-AS1 levels. The significance of these levels in the patients' postoperative prognosis was evaluated via logistic regression and ROC analyses, with a follow-up period of six months. Results: FAM83A-AS1 was significantly upregulated in NSCLC and correlated with severe progression in patients. Thoracotomy suppressed FAM83A-AS1 expression and reduced CA50, CEA, and CYFRA21-1 levels. Postoperative plasma levels of FAM83A-AS1 positively correlated with CA50, CEA, and CYFRA21-1. Patients with worse prognoses had higher plasma FAM83A-AS1 levels. FAM83A-AS1 was identified as a risk factor for poor postoperative outcomes in NSCLC patients undergoing thoracotomy and could be used to identify patients at risk of worse prognosis. Conclusion: An increase in FAM83A-AS1 in NSCL indicates severe disease development and can serve as a biomarker associated with thoracotomy, predicting a poor prognosis. It provides a potential indicator for patient outcomes. [ABSTRACT FROM AUTHOR]

Interferon-induced protein 44-like (IFI44L) is regarded as an immune-related gene and is a member of interferon-stimulated genes (ISGs). They participate in network transduction, and its own epigenetic modifications, apoptosis, cell-matrix formation, and many other pathways in tumors, autoimmune diseases, and viral infections. The current review provides a comprehensive overview of the onset and biological mechanisms of IFI44L and its potential clinical applications in malignant tumors and non-neoplastic diseases. [ABSTRACT FROM AUTHOR]

It is crucial to identify the metabolic risk factors of cerebral small vessel disease (CSVD) and implement timely and systematic management. Currently, the correlation between residual metabolic risk factors and CSVD is still controversial, and there’s a lack of evidence-based support for the clinical efficacy of targeting risk factors in treating CSVD. This paper comprehensively analyzes the correlation between residual metabolic risk factors such as inflammation, gut microbiota dysbiosis, hyperhomocysteinemia, and hyperuricemia with the occurrence and development of CSVD. It further explores potential therapeutic options targeting metabolic risk factors, emphasizes the important role of metabolomics in the discovery of novel metabolic biomarkers and the establishment of risk prediction models for CSVD, and looks forward to future research directions, to provide a theoretical basis for the early diagnosis, mechanism exploration, risk factor management, and comprehensive multidisciplinary management of CSVD. [ABSTRACT FROM AUTHOR]

UBE2C (Ubiquitination-binding enzyme 2C), one of the E2 enzymes encoded in the human genome, is a component of the ubiquitin proteasome system and plays a pivotal role in regulating cell cycle progression. Moreover, UBE2C is highly expressed and may play a pivotal role in both high-incidence and high-mortality malignancies, including lung cancers, breast cancers, and esophageal cancers. UBE2C influences a number of key processes, including cell cycle progression, tumor invasion and metastasis, proliferation, and drug resistance. However, few articles have systematically summarized the role of UBE2C in cancer. The aim of this review is to describe the structure and function of UBE2C, focusing on the current status of UBE2C research in malignant tumors. Furthermore, this review presents the potential of UBE2C as a new therapeutic target and a diagnostic and prognostic biomarker. Finally, future research directions for UBE2C are proposed. It is of great value to explore the mechanism of action of UBE2C in the tumor microenvironment (TME). A comprehensive and coherent comprehension of UBE2C will undoubtedly facilitate its transition from fundamental research to clinical applications. [ABSTRACT FROM AUTHOR]

Objective: To explore the complex mechanisms of keloid, new approaches have been developed by different strategies. However, conventional treatment did not significantly reduce the recurrence rate. This study aimed to identify new biomarkers and mechanisms for keloid progression through bioinformatics analyses. Methods: In our study, microarray datasets for keloid were downloaded from the GEO database. Differentially expressed genes (DEGs) were identified by R software. Multiple bioinformatics tools were used to identify hub genes, and reverse predict upstream miRNAs and lncRNA molecules of target hub genes. Finally, the total RNA-sequencing technique and miRNA microarray were combined to validate the identified genes. Results: Thirty-one DEGs were screened out and the upregulated hub gene SPP1 was finally identified, which was consistent with our RNA-sequencing analysis results and validation dataset. In addition, a ceRNA network of mRNA (SPP1)-miRNA (miR-181a-5p)-lncRNA (NEAT1, MALAT1, LINC00667, NORAD, XIST and MIR4458HG) was identified by the bioinformatics databases. The results of our miRNA microarray showed that miR-181a-5p was upregulated in keloid, also we found that the lncRNA NEAT1 could affect keloid progression by retrieving the relevant literature. Conclusions: We speculate that SPP1 is a potential candidate biomarker and therapeutic target for patients with keloid, and NEAT1/miR-181a-5p/SPP1 might be the RNA regulatory pathway that regulates keloid formation. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are the primary cause of death globally. The evolution of nearly all types of CVDs is characterized by a common theme: the emergence of cardiac fibrosis. The precise mechanisms that trigger cardiac fibrosis are still not completely understood. In recent years, a type of non-coding regulatory RNA molecule known as circular RNAs (circRNAs) has been reported. These molecules are produced during back splicing and possess significant biological capabilities, such as regulating microRNA activity, serving as protein scaffolds and recruiters, competing with mRNA, forming circR-loop structures to modulate transcription, and translating polypeptides. Furthermore, circRNAs exhibit a substantial abundance, notable stability, and specificity of tissues, cells, and time, endowing them with the potential as biomarkers, therapeutic targets, and therapeutic agents. CircRNAs have garnered growing interest in the field of CVDs. Recent investigations into the involvement of circRNAs in cardiac fibrosis have yielded encouraging findings. This study aims to provide a concise overview of the existing knowledge about the regulatory roles of circRNAs in cardiac fibrosis.

Abstract Background Hepatocellular carcinoma (HCC) is a malignant tumor characterized by a high mortality rate. The occurrence and progression of HCC are linked to oxidative stress. Glyoxalase-1 (GLO1) plays an important role in regulating oxidative stress, yet the underlying mechanism remains unclear. GLO1 may serve as a prognostic biomarker and therapeutic target for HCC. Methods Based on TCGA database hepatocellular carcinoma samples, we conducted a bioinformatics analysis to explore the correlation between GLO1 expression and HCC cell proliferation and viability. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that differentially expressed genes (DEGs) were mainly enriched in the cell cycle pathway. We analyzed the relationships between GLO1 and 24 genes enriched in the cell cycle pathway using a protein-protein interaction (PPI) network. Finally, experimental validation was performed to assess GLO1’s impact on the distribution of cells at different cell cycle stages and on the proliferation and migration of HCC cells. Results Our study demonstrated that GLO1 was overexpressed in HCC tissues and was associated with a poor prognosis. Data analysis indicated that overexpression of GLO1 activated the cell cycle pathway and positively correlated with expression of the majority of key cell cycle genes. Experimental validation showed that GLO1 expression affects the number of HCC cells in G2 and S phases and regulates HCC cell proliferation and migration. Conclusions GLO1 represents a promising therapeutic target for HCC, providing valuable insights into its role in the viability and proliferation of HCC cells.

From a global perspective, cardiovascular diseases (CVDs), the leading factor accounting for population mortality, and circRNAs, RNA molecules with stable closed-loop structures, have been proven to be closely related. The latent clinical value and the potential role of circRNAs in CVDs have been attracting increasing, active research interest, but bibliometric studies in this field are still lacking. Thus, in this study, we conducted a bibliometric analysis by using software such as VOSviewer, CiteSpace, Microsoft Excel, and the R package to determine the current research progress and hotspots and ultimately provide an overview of the development trends and future frontiers in this field. In our study, based on our search strategy, a total of 1206 publications published before July 31, 2023 were accessed from the WOSCC database. According to our findings, there is a notable increasing trend in global publications in the field of circRNA in CVDs. China was found to be the dominant country in terms of publication number, but a lack of high-quality articles was a significant fault. A cluster analysis on the co-cited references indicated that dilated cardiomyopathy, AMI, and cardiac hypertrophy are the greatest objects of concern. In contrast, a keywords analysis indicated that high importance has been ascribed to MI, abdominal aortic aneurysm, cell proliferation, and coronary artery diseases.

Yiming Zhou,1 Rui Chai,2 Yongxiang Wang,3 Xiaojun Yu3 1Department of Hepatopancreatobiliary Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, People’s Republic of China; 2General Surgery, Cancer Center, Department of Colorectal Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, People’s Republic of China; 3Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, People’s Republic of ChinaCorrespondence: Xiaojun Yu, Email fishyocat@163.comBackground: EIF3D, a key component of the eukaryotic translation initiation factor 3 (EIF3) complex, is critical in selectively translating mRNAs with atypical cap structures. Its relationship with colon adenocarcinoma (COAD) development and immune infiltration, however, remains under-explored. This study delves into EIF3D’s role in COAD using bioinformatics and in vitro experimentation.Materials and Methods: We analyzed EIF3D expression levels utilizing TCGA, GTEx, CPTAC, and TISIDB databases. The TISCH database and ssGSEA method helped in assessing EIF3D’s link with the tumor immune microenvironment. EIF3D expression in CRC cells was gauged via real-time PCR. Cell proliferation was assessed using CCK8 and colony formation assays, while migration capabilities were tested through Transwell assays. Flow cytometry facilitated cell cycle distribution and apoptosis analysis. ChIP-qPCR identified transcription factors regulating EIF3D, and bulk sequencing explored EIF3D’s pathways in promoting COAD.Results: EIF3D upregulation is a common feature in various tumors, especially in COAD, correlating with poor prognosis in many cancer types. It showed significant associations with immune cell and cancer-associated fibroblast (CAF) infiltration across multiple tumors. Additionally, it is closely associated with molecular and immune subtypes of multiple tumors, including COAD. Single-cell analyses depicted EIF3D’s distribution and proportion in CRC immune cells. In vitro findings indicated EIF3D knockdown curtailed proliferation and migration, inducing G0/G1 arrest in COAD cells. Moreover, bulk sequencing revealed EIF3D knockdown interferes with multiple cancer-related pathways, likely by curtailing cell cycle and DNA replication activities to regulate cell proliferation.Conclusion: EIF3D emerges as a potential prognostic biomarker for tumor progression and immune infiltration, particularly in COAD, potentially predicting immunotherapy efficacy. Additionally, EIF3D represents a multifaceted target implicated in COAD’s malignant progression.Keywords: EIF3D, pan-cancer, tumor immune microenvironment, biomarker, therapeutic target

Urological malignant tumors pose a significant threat to human health, with a high incidence rate each year. Prostate cancer, bladder cancer, and renal cell carcinoma are among the most prevalent and extensively researched urological malignancies. Despite advancements in research, the prognosis for these tumors remains unfavorable due to late detection, postoperative recurrence, and treatment resistance. A thorough investigation into their pathogenesis is crucial for early diagnosis and treatment. Recent studies have highlighted the close association between microRNAs (miRNAs) and cancer progression. miRNAs are small non-coding RNAs composed of 19-23 nucleotides that regulate gene expression by binding to the 3' untranslated region (3'UTR) of target mRNAs, impacting key cellular processes such as proliferation, differentiation, apoptosis, and migration. Dysregulation of miRNAs can disrupt the expression of oncogenes and tumor suppressor genes, contributing to cancer development. Among the various miRNAs studied, miR-152 has garnered attention for its role in urological malignancies. Several studies have indicated that dysregulation of miR-152 expression is significant in these cancers, warranting a comprehensive review of the evidence. This review focuses on the expression and function of miR-152 in prostate cancer, bladder cancer, and renal cell carcinoma, elucidating its mechanisms in cancer progression and exploring its potential as a therapeutic target and biomarker in urological malignancies. [ABSTRACT FROM AUTHOR]

• SHTN1 had been demonstrated for the first time as a diagnostic and prognostic marker for bladder cancer. • SHTN1 was shown for the first time to be more highly expressed in high-grade bladder cancer. and to be associated with immune cells and the tumor microenvironment. • It had been demonstrated for the first time SHTN1 was associated with immune cells and the tumor microenvironment. Gene therapy in bladder cancer (BLCA) remains an area ripe for exploration. Recent studies have highlighted the crucial role of SHTN1 in the initiation and progression of various cancers and SHTN1 may have interacted with the FGFR gene. However, its specific function in BLCA remains unclear. We investigated the association between SHTN1 expression and prognosis, immune infiltration, and the tumor microenvironment (TME) across multiple malignancies using 433 BLCA samples from The Cancer Genome Atlas (TCGA). Differential gene expression analysis, functional annotation via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed for SHTN1-related genes by using R packages. Immune response and TME scores, along with drug sensitivity profiles of SHTN1, were analyzed using R packages. Immunohistochemistry (IHC) and western blotting were conducted to assess SHTN1 expression in surgical specimens from BLCA patients.CCK8 assay and cells wound healing assay were performed.The bioinformatics was analyzed by R software. Significant differences were evaluated using unpaired t test. SHTN1 expression levels were significantly elevated in BLCA associated with poor prognosis (p < 0.01). Receiver operating characteristic (ROC) curves and nomograms demonstrated the diagnostic and prognostic efficacy of SHTN1 in BLCA. Notably, SHTN1 expression was higher in high-grade BLCA compared to lower-grade (p = 5.6e-10), a finding corroborated by IHC and western blotting. Pathway enrichment analysis revealed significant involvement of the Neuroactive ligand-receptor interaction and Chemical carcinogenesis - DNA adducts signaling pathways among SHTN1 differentially expressed genes. In terms of immune infiltration, T cells CD8, T cells follicular helper, and dendritic cells were predominant in the SHTN1 low-expression group, whereas macrophages M0 and M2, and mast cells were predominant in the high-expression group. Multivariate Cox regression analysis identified SHTN1 as an independent prognostic factor for overall survival (HR = 2.93; 95 % CI = 1.40–6.13; p = 0.004).CCK8 and wound healing experiments showed that SHTN1 knockdown reduced the cell proliferation and migration. Western blot showed that the EMT pathway was clearly associated with SHTN1. Our findings suggest that SHTN1 holds promise as a prognostic and diagnostic biomarker for BLCA. Moreover, it is closely associated with elevated immune infiltration and distinct characteristics of the tumor microenvironment in BLCA. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a highly aggressive type of breast cancer that encompasses several distinct subtypes. Recent advances in immunotherapy offer a promising future for the treatment of these highly heterogeneous and readily metastatic tumors. Despite advancements, the efficacy of immunotherapy remains limited as shown by unimproved efficacy of PD-L1 biomarker and limited patient benefit. To enhance the effectiveness of TNBC immunotherapy, we conducted investigation on the microenvironment, and corresponding therapeutic interventions of TNBC and recommended further investigation into the identification of additional biomarkers that can facilitate the subtyping of TNBC for more targeted therapeutic approaches. TNBC is a highly aggressive subtype with dismal long-term survival due to the lack of opportunities for traditional endocrine and targeted therapies. Recent advances in immunotherapy have shown promise, but response rates can be limited due to the heterogeneous tumor microenvironments and developed therapy resistance, especially in metastatic cases. In this review, we will investigate the tumor microenvironment of TNBC and corresponding therapeutic interventions. We will summarize current subtyping strategies and available biomarkers for TNBC immunotherapy, with a particular emphasis on the need for further research to identify additional prognostic markers and refine tailored therapies for specific TNBC subtypes. These efforts aim to improve treatment sensitivity and ultimately enhance survival outcomes for advancedstage TNBC patients. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a malignant tumor characterized by a high mortality rate. The occurrence and progression of HCC are linked to oxidative stress. Glyoxalase-1 (GLO1) plays an important role in regulating oxidative stress, yet the underlying mechanism remains unclear. GLO1 may serve as a prognostic biomarker and therapeutic target for HCC. Methods: Based on TCGA database hepatocellular carcinoma samples, we conducted a bioinformatics analysis to explore the correlation between GLO1 expression and HCC cell proliferation and viability. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that differentially expressed genes (DEGs) were mainly enriched in the cell cycle pathway. We analyzed the relationships between GLO1 and 24 genes enriched in the cell cycle pathway using a protein-protein interaction (PPI) network. Finally, experimental validation was performed to assess GLO1's impact on the distribution of cells at different cell cycle stages and on the proliferation and migration of HCC cells. Results: Our study demonstrated that GLO1 was overexpressed in HCC tissues and was associated with a poor prognosis. Data analysis indicated that overexpression of GLO1 activated the cell cycle pathway and positively correlated with expression of the majority of key cell cycle genes. Experimental validation showed that GLO1 expression affects the number of HCC cells in G2 and S phases and regulates HCC cell proliferation and migration. Conclusions: GLO1 represents a promising therapeutic target for HCC, providing valuable insights into its role in the viability and proliferation of HCC cells. [ABSTRACT FROM AUTHOR]

Coactivator-associated arginine methyltransferase 1 (CARM1), pivotal for catalyzing arginine methylation of histone and non-histone proteins, plays a crucial role in developing various cancers. CARM1 was initially recognized as a transcriptional coregulator by orchestrating chromatin remodeling, transcription regulation, mRNA splicing and stability. This diverse functionality contributes to the recruitment of transcription factors that foster malignancies. Going beyond its established involvement in transcriptional control, CARM1-mediated methylation influences a spectrum of biological processes, including the cell cycle, metabolism, autophagy, redox homeostasis, and inflammation. By manipulating these physiological functions, CARM1 becomes essential in critical processes such as tumorigenesis, metastasis, and therapeutic resistance. Consequently, it emerges as a viable target for therapeutic intervention and a possible biomarker for medication response in specific cancer types. This review provides a comprehensive exploration of the various physiological functions of CARM1 in the context of cancer. Furthermore, we discuss potential CARM1-targeting pharmaceutical interventions for cancer therapy. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDDs) are a diverse group of neurological disorders characterized by alterations in the structure and function of the central nervous system. Alzheimer's disease (AD), characterized by impaired memory and cognitive abilities, is the most prevalent type of senile dementia. Loss of synapses, intracellular aggregation of hyperphosphorylated tau protein, and extracellular amyloid-β peptide (Aβ) plaques are the hallmarks of AD. MicroRNAs (miRNAs/miRs) are single-stranded ribonucleic acid (RNA) molecules that bind to the 3′ and 5′ untranslated regions of target genes to cause post-transcriptional gene silencing. The brain expresses over 70% of all experimentally detected miRNAs, and these miRNAs are crucial for synaptic function and particular signals during memory formation. Increasing evidence suggests that miRNAs play a role in AD pathogenesis and we provide an overview of the role of miRNAs in synapse formation, Aβ synthesis, tau protein accumulation, and brain-derived neurotrophic factor-associated AD pathogenesis. We further summarize and discuss the role of miRNAs as potential therapeutic targets and biomarkers for AD detection and differentiation between early- and late-stage AD, based on recent research. In conclusion, altered expression of miRNAs in the brain and peripheral circulation demonstrates their potential as biomarkers and therapeutic targets in AD. [ABSTRACT FROM AUTHOR]

Lung cancer is a prevalent malignancy and the leading cause of cancer-related deaths, posing a significant threat to human health. Despite advancements in treatment, the prognosis for lung cancer patients remains poor due to late diagnosis, cancer recurrence, and drug resistance. Epigenetic research, particularly in microRNAs, has introduced a new avenue for cancer prevention and treatment. MicroRNAs, including miR-137, play a vital role in tumor development by regulating various cellular processes. MiR-137 has garnered attention for its tumor-suppressive properties, with studies showing its potential in inhibiting cancer progression. In lung cancer, miR-137 is of particular interest, with numerous reports exploring its role and mechanisms. A comprehensive review is necessary to consolidate current evidence. This review highlights recent studies on miR-137 in lung cancer, covering cell proliferation, migration, apoptosis, drug resistance, and therapy, emphasizing its potential as a biomarker and therapeutic target for lung cancer treatment and prognosis. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are non-coding RNAs that exist naturally in various eukaryotic organisms. The majority of circRNAs are produced through the splicing of exons, although there are a limited number that are generated through the circularization of introns. Studies have shown that circRNAs play an irreplaceable role in the pathogenesis, disease progression, diagnosis, and targeted therapy of motor system tumors (osteosarcoma), metabolic diseases (osteoporosis), and degenerative diseases (osteonecrosis of the femoral head, osteoarthritis, intervertebral disc degeneration). This review summarizes the advancements in circRNA detection techniques and the research progress of circRNAs in orthopedic diseases.

Long non-coding RNAs (lncRNAs) are crucial regulatory molecules that participate in numerous cellular development processes, and they have gathered much interest recently. HOXA10 antisense RNA (HOXA10-AS, also known as HOXA-AS4) is a novel lncRNA that was identified to be dysregulated in some prevalent malignancies. In this review, the clinical significance of HOXA10-AS for the prognosis of various cancers is analyzed. In addition, the major advances in our understanding of the cellular biological functions and mechanisms of HOXA10-AS in different human cancers are summarized. These cancers include esophageal carcinoma (ESCA), gastric cancer (GC), glioma, laryngeal squamous cell carcinoma (LSCC), acute myeloid leukemia (AML), lung adenocarcinoma (LUAD), nasopharyngeal carcinoma (NPC), oral squamous cell carcinoma (OSCC), and pancreatic cancer. We also note that the aberrant expression of HOXA10-AS promotes malignant progression through various underlying mechanisms. In conclusion, HOXA10-AS is expected to serve as an ideal clinical biomarker and an effective cancer therapy target.

Interferon-induced protein 44-like (IFI44L) is regarded as an immune-related gene and is a member of interferon-stimulated genes (ISGs). They participate in network transduction, and its own epigenetic modifications, apoptosis, cell-matrix formation, and many other pathways in tumors, autoimmune diseases, and viral infections. The current review provides a comprehensive overview of the onset and biological mechanisms of IFI44L and its potential clinical applications in malignant tumors and non-neoplastic diseases.

Progranulin (PGRN), a multifunctional growth factor-like protein expressed by a variety of cell types, serves an important function in the physiologic and pathologic processes of fibrotic diseases, including wound healing and the inflammatory response. PGRN was discovered to inhibit pro-inflammation effect by competing with tumor necrosis factor-alpha (TNF-α) binding to TNF receptors. Notably, excessive tissue repair in the development of inflammation causes tissue fibrosis. Previous investigations have indicated the significance of PGRN in regulating inflammatory responses. Recently, multiple studies have shown that PGRN was linked to fibrogenesis, and was considered to monitor the formation of fibrosis in multiple organs, including liver, cardiovascular, lung and skin. This paper is a comprehensive review summarizing our current knowledge of PGRN, from its discovery to the role in fibrosis. This is followed by an in-depth look at the characteristics of PGRN, consisting of its structure, basic function and intracellular signaling. Finally, we will discuss the potential of PGRN in the diagnosis and treatment of fibrosis.

Abstract Modern human society is burdened with the pandemic of cardiovascular and metabolic diseases. Metrnl is a widely distributed secreted protein in the body, involved in regulating glucose and lipid metabolism and maintaining cardiovascular system homeostasis. In this review, we present the predictive and therapeutic roles of Metrnl in various cardiovascular and metabolic diseases, including atherosclerosis, ischemic heart disease, cardiac remodeling, heart failure, hypertension, chemotherapy-induced myocardial injury, diabetes mellitus, and obesity.

Abstract Objective Gastric cancer (GC) is one of the most common malignancies worldwide and it is considered the fourth most common cause of cancer death. This study aimed to find critical genes/pathways in GC pathogenesis to be used as biomarkers or therapeutic targets. Methods Differentially expressed genes were explored between human gastric cancerous and noncancerous tissues, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analyses were done. Hub genes were identified based on the protein–protein interaction network constructed in the STRING database with Cytoscape software. The hub genes were selected for further investigation using GEPIA2 and DrugBank databases. Results Ten overexpressed hub genes in GC were identified in the current study, including FN1, TP53, IL-6, CXCL5, ELN, ADAMTS2, WISP1, MMP2, CTGF, and THBS1. The study demonstrated the PI3K-Akt pathway's central involvement in GC, with pronounced alterations in essential components. Survival analysis revealed significant correlations between CTGF, FN1, IL-6, THBS1, and WISP1 overexpression and reduced overall survival times in GC patients. Conclusion A mutual interplay emerged, where PI3K-Akt signaling could upregulate certain genes, forming feedback loops and intensifying cancer phenotypes. The interconnected overexpression of genes and the PI3K-Akt pathway fosters gastric tumorigenesis, suggesting therapeutic potential. DrugBank analysis identified limited FDA-approved drugs, advocating for further exploration while targeting these hub genes could reshape GC treatment. The identified genes could be novel diagnostic/prognostic biomarkers or potential therapeutic targets for GC, but further clinical validation is required.

Abstract 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.

Objective: Gastric cancer (GC) is one of the most common malignancies worldwide and it is considered the fourth most common cause of cancer death. This study aimed to find critical genes/pathways in GC pathogenesis to be used as biomarkers or therapeutic targets. Methods: Differentially expressed genes were explored between human gastric cancerous and noncancerous tissues, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analyses were done. Hub genes were identified based on the protein–protein interaction network constructed in the STRING database with Cytoscape software. The hub genes were selected for further investigation using GEPIA2 and DrugBank databases. Results: Ten overexpressed hub genes in GC were identified in the current study, including FN1, TP53, IL-6, CXCL5, ELN, ADAMTS2, WISP1, MMP2, CTGF, and THBS1. The study demonstrated the PI3K-Akt pathway's central involvement in GC, with pronounced alterations in essential components. Survival analysis revealed significant correlations between CTGF, FN1, IL-6, THBS1, and WISP1 overexpression and reduced overall survival times in GC patients. Conclusion: A mutual interplay emerged, where PI3K-Akt signaling could upregulate certain genes, forming feedback loops and intensifying cancer phenotypes. The interconnected overexpression of genes and the PI3K-Akt pathway fosters gastric tumorigenesis, suggesting therapeutic potential. DrugBank analysis identified limited FDA-approved drugs, advocating for further exploration while targeting these hub genes could reshape GC treatment. The identified genes could be novel diagnostic/prognostic biomarkers or potential therapeutic targets for GC, but further clinical validation is required. [ABSTRACT FROM AUTHOR]

Progranulin (PGRN), a multifunctional growth factor-like protein expressed by a variety of cell types, serves an important function in the physiologic and pathologic processes of fibrotic diseases, including wound healing and the inflammatory response. PGRN was discovered to inhibit pro-inflammation effect by competing with tumor necrosis factor-alpha (TNF- α) binding to TNF receptors. Notably, excessive tissue repair in the development of inflammation causes tissue fibrosis. Previous investigations have indicated the significance of PGRN in regulating inflammatory responses. Recently, multiple studies have shown that PGRN was linked to fibrogenesis, and was considered to monitor the formation of fibrosis in multiple organs, including liver, cardiovascular, lung and skin. This paper is a comprehensive review summarizing our current knowledge of PGRN, from its discovery to the role in fibrosis. This is followed by an in-depth look at the characteristics of PGRN, consisting of its structure, basic function and intracellular signaling. Finally, we will discuss the potential of PGRN in the diagnosis and treatment of fibrosis. Progranulin (PGRN) is a promising biomarker and therapeutic target for fibrotic diseases. PGRN can act both as a pro-fibrotic and as anti-fibrotic factor in several fibrotic diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Modern human society is burdened with the pandemic of cardiovascular and metabolic diseases. Metrnl is a widely distributed secreted protein in the body, involved in regulating glucose and lipid metabolism and maintaining cardiovascular system homeostasis. In this review, we present the predictive and therapeutic roles of Metrnl in various cardiovascular and metabolic diseases, including atherosclerosis, ischemic heart disease, cardiac remodeling, heart failure, hypertension, chemotherapy-induced myocardial injury, diabetes mellitus, and obesity. [ABSTRACT FROM AUTHOR]

Circular RNAs are a class of noncoding RNAs with covalently linked 5′ and 3′ ends that arise from backsplicing events. The absence of a 5′ cap and a 3′ poly(A) tail makes circular RNAs relatively more stable than their linear counterparts. They are evolutionary conserved and tissue‐specific, and some show disease‐specific expression patterns. Although their biological functions remain largely unknown, circular RNAs have been shown to play regulatory roles by acting as microRNA sponges, regulators of RNA‐binding proteins, alternative splicing, and parental gene expression, and they could even encode proteins. Over the past few decades, circular RNAs have attracted wide attention in oncology owing to their implications in various tumors. Many circular RNAs have been characterized as key players in gastrointestinal cancers and influence cancer growth, progression, metastasis, and therapeutic resistance. Accumulating evidence reveals that their unique characteristics, coupled with their critical roles in tumorigenesis, make circular RNAs promising non‐invasive clinical biomarkers for gastrointestinal cancers. In the present review, we summarized the biological roles of the emerging circular RNAs and their potential as biomarkers and therapeutic targets, which may help better understand their clinical significance in the management of gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Dysregulation of long non-coding RNA (lncRNA) HOXA-AS3 has been shown to contribute to the development of multiple cancer types. Several studies have presented the tumour-modulatory role or prognostic significance of this lncRNA in various kinds of cancer. Overall, HOXA-AS3 can act as a competing endogenous RNA (ceRNA) that inhibits the activity of seven microRNAs (miRNAs), including miR-29a-3p, miR-29 b-3p, miR-29c, miR-218–5p, miR-455–5p, miR-1286, and miR-4319. This relieves the downstream messenger RNA (mRNA) targets of these miRNAs from miRNA-mediated translational repression, allowing them to exert their effect in regulating cellular activities. Examples of the pathways regulated by lncRNA HOXA-AS3 and its associated downstream targets include the WNT/β-catenin and epithelial-to-mesenchymal transition (EMT) activities. Besides, HOXA-AS3 can interact with other cellular proteins like homeobox HOXA3 and HOXA6, influencing the oncogenic signaling pathways associated with these proteins. Generally, HOXA-AS3 is overexpressed in most of the discussed human cancers, making this lncRNA a potential candidate to diagnose cancer or predict the clinical outcomes of cancer patients. Hence, targeting HOXA-AS3 could be a new therapeutic approach to slowing cancer progression or as a potential biomarker and therapeutic target. A drawback of using lncRNA HOXA-AS3 as a biomarker or therapeutic target is that most of the studies that have reported the tumour-regulatory roles of lncRNA HOXA-AS3 are single observational, in vitro , or in vivo studies. More in-depth mechanistic and large-scale clinical trials must be conducted to confirm the tumour-modulatory roles of lncRNA HOXA-AS3 further. Besides, no lncRNA HOXA-AS3 inhibitor has been tested preclinically and clinically, and designing such an inhibitor is crucial as it may potentially slow cancer progression. • LncRNA HOXA-AS3 was correlated with the tumour-modulatory role. • HOXA-AS3 contribute to the development of cancer via inhibition of several miRNA or protein. • It can be translated as potential clinical target for diagnostic, prognostic, and treatment of cancer. [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]

Neuropilin 2 (NRP2), a transmembrane non-tyrosine kinase receptor, has been described as a potential critical player in the tumourigenesis of several solid cancers and particularly in neuroendocrine neoplasms (NENs). A soluble form of NRP2 (sNRP2) has been previously described and corresponds to a truncated splice isoform. Its prognostic value has never been studied in NEN. NRP2 expression was studied by immunochemistry on tissue microarrays (n = 437) and on circulating tumour cells (CTCs, n = 5 patients with neuroendocrine carcinoma, NEC). We described the levels of sNRP2 in 229 patients with NEN using the ELISA method to identify the factors associated with sNRP2 levels and to evaluate its prognostic role; 90 blood donors represented the healthy control group. NRP2 was found in 97% of neuroendocrine tumours (396/410) and in 74% of NEC (20/27). NRP2 was also expressed in CTC of all the studied patients. The receiver operating characteristic (ROC) analysis showed that sNRP2 had a weak capacity to discriminate between NEN patients and healthy controls (area under curve (AUC) = 0.601, P = 0.053). Abnormal sNRP2 levels were associated with inflammatory syndrome, bone and peritoneal metastases, and abnormal chromogranin A levels. Patients with high sNRP2 levels (sNRP2Q3-Q4) had significantly poorer overall survival in multivariate analysis (HR 0.16, 95% CI (0.04-0.67), P = 0.015). In conclusion, the present study found that sNRP2 and NRP2 could represent a new prognostic biomarker and a therapeutic target, respectively, particularly in aggressive NEN. [ABSTRACT FROM AUTHOR]

Urological malignant tumors pose a significant threat to human health, with a high incidence rate each year. Prostate cancer, bladder cancer, and renal cell carcinoma are among the most prevalent and extensively researched urological malignancies. Despite advancements in research, the prognosis for these tumors remains unfavorable due to late detection, postoperative recurrence, and treatment resistance. A thorough investigation into their pathogenesis is crucial for early diagnosis and treatment. Recent studies have highlighted the close association between microRNAs (miRNAs) and cancer progression. miRNAs are small non-coding RNAs composed of 19-23 nucleotides that regulate gene expression by binding to the 3’ untranslated region (3’UTR) of target mRNAs, impacting key cellular processes such as proliferation, differentiation, apoptosis, and migration. Dysregulation of miRNAs can disrupt the expression of oncogenes and tumor suppressor genes, contributing to cancer development. Among the various miRNAs studied, miR-152 has garnered attention for its role in urological malignancies. Several studies have indicated that dysregulation of miR-152 expression is significant in these cancers, warranting a comprehensive review of the evidence. This review focuses on the expression and function of miR-152 in prostate cancer, bladder cancer, and renal cell carcinoma, elucidating its mechanisms in cancer progression and exploring its potential as a therapeutic target and biomarker in urological malignancies.

Abstract Liver disease is a complex group of diseases with high morbidity and mortality rates, emerging as a major global health concern. Recent studies have highlighted the involvement of fibrinogen-like proteins, specifically fibrinogen-like protein 1 (FGL1) and fibrinogen-like protein 2 (FGL2), in the regulation of various liver diseases. FGL1 plays a crucial role in promoting hepatocyte growth, regulating lipid metabolism, and influencing the tumor microenvironment (TME), contributing significantly to liver repair, non-alcoholic fatty liver disease (NAFLD), and liver cancer. On the other hand, FGL2 is a multifunctional protein known for its role in modulating prothrombin activity and inducing immune tolerance, impacting viral hepatitis, liver fibrosis, hepatocellular carcinoma (HCC), and liver transplantation. Understanding the functions and mechanisms of fibrinogen-like proteins is essential for the development of effective therapeutic approaches for liver diseases. Additionally, FGL1 has demonstrated potential as a disease biomarker in radiation and drug-induced liver injury as well as HCC, while FGL2 shows promise as a biomarker in viral hepatitis and liver transplantation. The expression levels of these molecules offer exciting prospects for disease assessment. This review provides an overview of the structure and roles of FGL1 and FGL2 in different liver conditions, emphasizing the intricate molecular regulatory processes and advancements in targeted therapies. Furthermore, it explores the potential benefits and challenges of targeting FGL1 and FGL2 for liver disease treatment and the prospects of fibrinogen-like proteins as biomarkers for liver disease, offering insights for future research in this field.

Liver disease is a complex group of diseases with high morbidity and mortality rates, emerging as a major global health concern. Recent studies have highlighted the involvement of fibrinogen-like proteins, specifically fibrinogen-like protein 1 (FGL1) and fibrinogen-like protein 2 (FGL2), in the regulation of various liver diseases. FGL1 plays a crucial role in promoting hepatocyte growth, regulating lipid metabolism, and influencing the tumor microenvironment (TME), contributing significantly to liver repair, non-alcoholic fatty liver disease (NAFLD), and liver cancer. On the other hand, FGL2 is a multifunctional protein known for its role in modulating prothrombin activity and inducing immune tolerance, impacting viral hepatitis, liver fibrosis, hepatocellular carcinoma (HCC), and liver transplantation. Understanding the functions and mechanisms of fibrinogen-like proteins is essential for the development of effective therapeutic approaches for liver diseases. Additionally, FGL1 has demonstrated potential as a disease biomarker in radiation and drug-induced liver injury as well as HCC, while FGL2 shows promise as a biomarker in viral hepatitis and liver transplantation. The expression levels of these molecules offer exciting prospects for disease assessment. This review provides an overview of the structure and roles of FGL1 and FGL2 in different liver conditions, emphasizing the intricate molecular regulatory processes and advancements in targeted therapies. Furthermore, it explores the potential benefits and challenges of targeting FGL1 and FGL2 for liver disease treatment and the prospects of fibrinogen-like proteins as biomarkers for liver disease, offering insights for future research in this field. [ABSTRACT FROM AUTHOR]

Due to the rapid development of RNA sequencing techniques, a circular noncoding RNA (ncRNA) known as circular RNAs (circRNAs) has gradually come into focus. As a distinguished member of the circRNA family, circ_0003945 has garnered attention for its aberrant expression and biochemical functions in human diseases. Subsequent studies have revealed that circ_0003945 could regulate tumor cells proliferation, migration, invasion, apoptosis, autophagy, angiogenesis, drug resistance, and radio resistance through the molecular mechanism of competitive endogenous RNA (ceRNA) during tumorigenesis. The expression of circ_0003945 is frequently associated with some clinical parameters and implies a poorer prognosis in the majority of cancers. In nonmalignant conditions, circ_0003945 also holds considerable importance in diseases pathogenesis. This review aims to recapitulate molecular mechanism of circ_0003945 and elucidates its potential as a diagnostic and therapeutic target in neoplasms and other diseases. [ABSTRACT FROM AUTHOR]

Brain metastasis is a significant challenge for some breast cancer patients, marked by its aggressive nature, limited treatment options, and poor clinical outcomes. Immunotherapies have emerged as a promising avenue for brain metastasis treatment. B7-H3 (CD276) is an immune checkpoint molecule involved in T cell suppression, which is associated with poor survival in cancer patients. Given the increasing number of clinical trials using B7-H3 targeting CAR T cell therapies, we examined B7-H3 expression across breast cancer subtypes and in breast cancer brain metastases to assess its potential as an interventional target. B7-H3 expression was investigated using immunohistochemistry on tissue microarrays of three clinical cohorts: (i) unselected primary breast cancers (n = 347); (ii) brain metastatic breast cancers (n = 61) and breast cancer brain metastases (n = 80, including a subset of 53 patient-matched breast and brain metastasis cases); and (iii) mixed brain metastases from a range of primary tumours (n = 137). In primary breast cancers, B7-H3 expression significantly correlated with higher tumour grades and aggressive breast cancer subtypes, as well as poorer 5-year survival outcomes. Subcellular localisation of B7-H3 impacted breast cancer-specific survival, with cytoplasmic staining also correlating with a poorer outcome. Its expression was frequently detected in brain metastases from breast cancers, with up to 90% expressing B7-H3. However, not all brain metastases showed high levels of expression, with those from colorectal and renal tumours showing a low frequency of B7-H3 expression (0/14 and 2/16, respectively). The prevalence of B7-H3 expression in breast cancers and breast cancer brain metastases indicates potential opportunities for B7-H3 targeted therapies in breast cancer management. [ABSTRACT FROM AUTHOR]

Skin Cutaneous Melanoma (SKCM) is a form of cancer that originates in the pigment‐producing cells, known as melanocytes, of the skin. Delay wound healing is often correlated with the occurrence of and progression of SKCM. In this comprehensive study, we investigated the intricate roles of two important wound healing genes in SKCM, including Matrix Metalloproteinase‐2 (MMP2) and Matrix Metalloproteinase‐9 (MMP9). Through a multi‐faceted approach, we collected clinical samples, conducted molecular experiments, including RT‐qPCR, bisulphite sequencing, cell culture, cell Counting Kit‐8, colony formation, and wound healing assays. Beside this, we also used various other databases/tools/approaches for additional analysis including, UALCAN, GEPIA, HPA, MEXPRESS, cBioPortal, KM plotter, DrugBank, and molecular docking. Our results revealed a significant up‐regulation of MMP2 and MMP9 in SKCM tissues compared to normal counterparts. Moreover, promoter methylation analysis suggested an epigenetic regulatory mechanism. Validations using TCGA datasets and immunohistochemistry emphasized the clinical relevance of MMP2 and MMP9 dysregulation. Functional assays demonstrated their synergistic impact on proliferation and migration in SKCM cells. Furthermore, we identified potential therapeutic candidates, Estradiol and Calcitriol, through drug prediction and molecular docking analyses. These compounds exhibited binding affinities, suggesting their potential as MMP2/MMP9 inhibitors. Overall, our study elucidates the diagnostic, prognostic, and therapeutic implications of MMP2 and MMP9 in SKCM, shedding light on their complex interplay in SKCM occurrence and progression. [ABSTRACT FROM AUTHOR]

Introduction: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. Mining differentially expressed genes of TNBC is helpful to explore new therapeutic targets. This study aimed to investigate diagnostic biomarker genes in TNBC compared to normal tissue. Additionally, we explored the functions and prognostic value of these key genes as well as potential targeted drugs that could affect these genes. Methods: Differential gene expression analysis was conducted using the R software with data from the Gene Expression Omnibus (GEO) database. Then, the identified differentially expressed genes (DEGs) were used to construct a protein-protein interaction (PPI) network using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. The mRNA expression levels of key genes were analyzed using the UALCAN database with data from The Cancer Genome Atlas (TCGA). Enrichment and survival analyses were performed using R software. In addition, potential compounds showing sensitivity to key genes were identified by gene set cancer analysis (GSCA). Results: Compared with normal tissues, a total of 203 DEGs were upregulated in TNBC. These DEGs participated in various biological processes including nuclear division, microtubule binding, cell cycle, and the p53 signaling pathway. Through the PPI network analysis, ten key genes were identified, among which four genes showed significant correlation with poor progression-free interval (PFI) in patients with TNBC. Moreover, the four survival-related genes were found to act as sensitive therapeutic targets. Conclusion: The identified four key genes were considered new biomarkers for diagnosis and prognosis and also potential therapeutic targets for TNBC. [ABSTRACT FROM AUTHOR]