{"title":"MicroRNA-501-3p targeting TM4SF1 facilitates tumor-related behaviors of gastric cancer cells via EMT signaling pathway","authors":"Yunhai Wei, Lei Yin, Xiao Xie, Zhongxin Wu, Jinyu Zhang, Yuhai Gao, Jianing Tang","doi":"10.1016/j.mrfmmm.2022.111802","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Increasing evidence shows that Transmembrane 4 L6 family member 1(TM4SF1) exerts a critical role in mediating the progression of various tumors. Nevertheless, the exact mechanism of TM4SF1 in gastric cancer (GC) remains unclear.</p></div><div><h3>Methods</h3><p>Bioinformatics analysis was utilized to analyze TM4SF1 expression in GC tissues. Also, MiRWalk and starBase databases were used to predict the upstream microRNAs<span><span> which could regulate TM4SF1 expression. Gene set enrichment analysis (GSEA) for TM4SF1 was conducted to screen the potentially involved pathways. Dysregulation of microRNA-501–3p/TM4SF1 was implemented to investigate the regulatory roles of these genes in GC. qRT-PCR and </span>western blot were employed to measure the expression changes of microRNA-501–3p, TM4SF1, and epithelial-mesenchymal transition (EMT) signaling pathway-associated proteins. CCK-8, colony formation, and transwell assays were introduced to examine the biological functions of GC cell lines.</span></p></div><div><h3>Results</h3><p>TM4SF1 presented a significantly low level in mRNA and protein in GC cells. MicroRNA-501–3p could target TM4SF1 and reduce its expression. Cell function experiments revealed that microRNA-501–3p facilitated cell proliferation, migration, and invasion, while inhibiting cell apoptosis in GC by targeting TM4SF1. EMT-associated proteins were altered by changing microRNA-501–3p/TM4SF1 axis.</p></div><div><h3>Conclusion</h3><p>MicroRNA-501–3p regulated EMT signaling pathway by down-regulating TM4SF1 expression and therefore facilitated the malignant progression of GC, which may provide a new potential therapeutic target for the treatment of GC patients.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111802"},"PeriodicalIF":1.5000,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S002751072200029X","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Increasing evidence shows that Transmembrane 4 L6 family member 1(TM4SF1) exerts a critical role in mediating the progression of various tumors. Nevertheless, the exact mechanism of TM4SF1 in gastric cancer (GC) remains unclear.
Methods
Bioinformatics analysis was utilized to analyze TM4SF1 expression in GC tissues. Also, MiRWalk and starBase databases were used to predict the upstream microRNAs which could regulate TM4SF1 expression. Gene set enrichment analysis (GSEA) for TM4SF1 was conducted to screen the potentially involved pathways. Dysregulation of microRNA-501–3p/TM4SF1 was implemented to investigate the regulatory roles of these genes in GC. qRT-PCR and western blot were employed to measure the expression changes of microRNA-501–3p, TM4SF1, and epithelial-mesenchymal transition (EMT) signaling pathway-associated proteins. CCK-8, colony formation, and transwell assays were introduced to examine the biological functions of GC cell lines.
Results
TM4SF1 presented a significantly low level in mRNA and protein in GC cells. MicroRNA-501–3p could target TM4SF1 and reduce its expression. Cell function experiments revealed that microRNA-501–3p facilitated cell proliferation, migration, and invasion, while inhibiting cell apoptosis in GC by targeting TM4SF1. EMT-associated proteins were altered by changing microRNA-501–3p/TM4SF1 axis.
Conclusion
MicroRNA-501–3p regulated EMT signaling pathway by down-regulating TM4SF1 expression and therefore facilitated the malignant progression of GC, which may provide a new potential therapeutic target for the treatment of GC patients.
期刊介绍：
Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs.
MR publishes articles in the following areas:
Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence.
The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance.
Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing.
Landscape of somatic mutations and epimutations in cancer and aging.
Role of de novo mutations in human disease and aging; mutations in population genomics.
Interactions between mutations and epimutations.
The role of epimutations in chromatin structure and function.
Mitochondrial DNA mutations and their consequences in terms of human disease and aging.
Novel ways to generate mutations and epimutations in cell lines and animal models.
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