Dataset Information

Long non-coding RNA SNHG4 promotes cervical cancer progression through regulating c-Met via targeting miR-148a-3p.

ABSTRACT: Long non-coding RNA (lncRNA) SNHG4 has been shown to be associated with the development of a variety of cancers. The purpose of this study was to investigate the effect of SNHG4 on cervical cancer (CC) and the corresponding mechanism. The qRT-PCR was used to determine the expressions of SNHG4 and miR-148a-3p in CC cell lines and tissues. Cell apoptosis and proliferation were measured by flow cytometry and MTT assay, respectively. The interaction between SNHG4, miR-148a-3p and c-Met was verified by bioinformatics, dual-luciferase reporter gene and RNA immunoprecipitation (RIP), and the effect of SNHG4 on the growth of CC tumor in vivo was explored. The expression of SNHG4 was increased in both CC cell lines and tissues, while the expression of miR-148a-3p was down-regulated. Meanwhile, silencing SNHG4 remarkably inhibited CC cell proliferation and promoted apoptosis. In addition, miR-148a-3p was a direct target gene of SNHG4, and down-regulation of miR-148a-3p could observably reverse the effect of silencing SNHG4 on the proliferation and apoptosis of CC cells. More importantly, SNHG4 could up-regulate the expression of c-Met by targeting and interacting with miR-148a-3p. Finally, in vivo experiments confirmed that silence SNHG4 down-regulated the expression of c-Met by promoting miR-148a-3p, and ultimately suppressed the growth of CC tumor in vivo. In conclusion, SNHG4 could be used as a competitive endogenous RNA to bind to miR-148a-3p, thereby up-regulating the expression of c-Met and ultimately promoting the progression of CC, which provided a potential therapeutic target for the targeted treatment of CC.

SUBMITTER: Li H

PROVIDER: S-EPMC6927695 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Long non-coding RNA SNHG4 promotes cervical cancer progression through regulating c-Met via targeting miR-148a-3p.

Li Hanchen H Hong Jiang J Wijayakulathilaka Walimuni Sandaroo Mendis Abeysekara WSMA

Cell cycle (Georgetown, Tex.) 20191007 23

Long non-coding RNA (lncRNA) SNHG4 has been shown to be associated with the development of a variety of cancers. The purpose of this study was to investigate the effect of SNHG4 on cervical cancer (CC) and the corresponding mechanism. The qRT-PCR was used to determine the expressions of SNHG4 and miR-148a-3p in CC cell lines and tissues. Cell apoptosis and proliferation were measured by flow cytometry and MTT assay, respectively. The interaction between SNHG4, miR-148a-3p ...[more]

PMID: 31590627

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Project description:Atherosclerosis (AS) seriously affects human health. The role of microRNAs (miRNAs) in the pathogenesis and progression of AS has become a focus of research. Our goal was to identify the biological effect of differentially expressed miRNAs (DE-miRNAs) in AS. To analyze differentially expressed genes (DEGs), including differentially expressed mRNAs (DE-mRNAs) and DE-miRNAs, in AS by using the Gene Expression Omnibus (GEO) database and limma package. DEGs protein-protein interaction (PPI) network and functional enrichment analysis were constructed by using the search tool for the retrieval of interacting genes/proteins (STRING) database, Cytoscape software and Cytoscape plugin "ClueGO2.5.6". We established a coexpression network of dysregulated miRNAs and mRNAs to predict the function of miRNAs by using miRWalk database and Pearson correlation coefficient (PCC) analysis. Cellular experiments were used to validate the results of bioinformatics. First, 69 common DEGs were obtained from datasets GSE43292 and GSE97210 using the limma package in R. Next, a DEG PPI network was constructed. Functional enrichment analysis of DEGs showed that 11 functional pathways were significantly enriched, such as positive regulation of monocyte chemotaxis. Seven common DE-miRNAs were obtained from the GSE99685 dataset and DE-mRNAs predicted miRNAs through the miRWalk database. The miRNA-mRNA network constructed using Cytoscape software suggested that miR-148a-3p targeted contactin 4 (CNTN4). Quantitative real-time polymerase chain reaction (qRT-PCR) assay results indicated that miR-148a-3p was downregulated and CNTN4 was upregulated in the THP-1 + phorbol 12-myristate 13-acetate (PMA) + oxidized low-density lipoprotein (oxLDL) group compared with the THP-1 + PMA group. qRT-PCR, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) found that upregulated miR-148a-3p significantly inhibited the expression of CNTN4, cell apoptosis, and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations in oxLDL-induced THP-1 macrophages. In addition, a dual-luciferase reporter assay demonstrated that CNTN4 was a target gene of miR-148a-3p. Overall, these findings suggested that miR-148a-3p inhibited oxLDL-induced cell apoptosis and inflammation via targeting CNTN4 in THP-1 macrophages.

Dataset Information

Long non-coding RNA SNHG4 promotes cervical cancer progression through regulating c-Met via targeting miR-148a-3p.

Publications

Long non-coding RNA <i>SNHG4</i> promotes cervical cancer progression through regulating c-Met via targeting miR-148a-3p.

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