{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen J"],"funding":["National Natural Science Foundation of China","Technology R&D Program of Suzhou"],"pagination":["69"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7014595"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["18(1)"],"pubmed_abstract":["BACKGROUND:Clear cell renal cell carcinoma (ccRCC) is one of the most aggressive urological malignancies. MicroRNAs (miRNAs) are post-transcriptional gene regulators in tumor pathophysiology. As miRNAs exert cooperative repressive effects on target genes, studying the miRNA synergism is important to elucidate the regulation mechanism of miRNAs. METHODS:We first created a miRNA-mRNA association network based on sequence complementarity and co-expression patterns of miRNA-targets. The synergism between miRNAs was then defined based on their expressional coherence and the concordance between target genes. The miRNA and mRNA expression were detected in RCC cell lines (786-O) using quantitative RT-PCR. Potential miRNA-target interaction was identified by Dual-Luciferase Reporter assay. Cell proliferation and migration were assessed by CCK-8 and transwell assay. RESULTS:A synergistic miRNA-miRNA interaction network of 28 miRNAs (52 miRNA pairs) with high coexpression level were constructed, among which miR-124 and miR-203 were identified as most tightly connected. ZEB2 expression is inversely correlated with miR-124 and miR-203 and verified as direct miRNA target. Cotransfection of miR-124 and miR-203 into 786-O cell lines effectively attenuated ZEB2 level and normalized renal cancer cell proliferation and migration. The inhibitory effects were abolished by ZEB2 knockdown. Furthermore, pathway analysis suggested that miR-124 and miR-203 participated in activation of epithelial-to-mesenchymal transition (EMT) pathway via regulation of ZEB2. CONCLUSIONS:Our findings provided insights into the role of miRNA-miRNA collaboration as well as a novel therapeutic approach in ccRCC."],"journal":["Journal of translational medicine"],"pubmed_title":["miR-124 and miR-203 synergistically inactivate EMT pathway via coregulation of ZEB2 in clear cell renal cell carcinoma (ccRCC)."],"pmcid":["PMC7014595"],"funding_grant_id":["SYN201614","SNG201905","21676173","31400712","31770903"],"pubmed_authors":["Chen J","Zhong Y","Li L"],"additional_accession":[]},"is_claimable":false,"name":"miR-124 and miR-203 synergistically inactivate EMT pathway via coregulation of ZEB2 in clear cell renal cell carcinoma (ccRCC).","description":"BACKGROUND:Clear cell renal cell carcinoma (ccRCC) is one of the most aggressive urological malignancies. MicroRNAs (miRNAs) are post-transcriptional gene regulators in tumor pathophysiology. As miRNAs exert cooperative repressive effects on target genes, studying the miRNA synergism is important to elucidate the regulation mechanism of miRNAs. METHODS:We first created a miRNA-mRNA association network based on sequence complementarity and co-expression patterns of miRNA-targets. The synergism between miRNAs was then defined based on their expressional coherence and the concordance between target genes. The miRNA and mRNA expression were detected in RCC cell lines (786-O) using quantitative RT-PCR. Potential miRNA-target interaction was identified by Dual-Luciferase Reporter assay. Cell proliferation and migration were assessed by CCK-8 and transwell assay. RESULTS:A synergistic miRNA-miRNA interaction network of 28 miRNAs (52 miRNA pairs) with high coexpression level were constructed, among which miR-124 and miR-203 were identified as most tightly connected. ZEB2 expression is inversely correlated with miR-124 and miR-203 and verified as direct miRNA target. Cotransfection of miR-124 and miR-203 into 786-O cell lines effectively attenuated ZEB2 level and normalized renal cancer cell proliferation and migration. The inhibitory effects were abolished by ZEB2 knockdown. Furthermore, pathway analysis suggested that miR-124 and miR-203 participated in activation of epithelial-to-mesenchymal transition (EMT) pathway via regulation of ZEB2. CONCLUSIONS:Our findings provided insights into the role of miRNA-miRNA collaboration as well as a novel therapeutic approach in ccRCC.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Feb","modification":"2020-05-22T10:29:16Z","creation":"2020-05-22T10:29:16Z"},"accession":"S-EPMC7014595","cross_references":{"pubmed":["32046742"],"doi":["10.1186/s12967-020-02242-x "]}}