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Updated: Apr 5, 2026
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
miR-200c Targets CDK2 and Suppresses Tumorigenesis in Renal Cell Carcinoma
Xuegang Wang1, Xuanyu Chen2, Weiwei Han2
1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China. Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, P.R. China.
Unlabelled:
miRNA expression profiles are widely investigated in the major cancers, but their specific roles and functions in cancers have not yet to be fully elucidated. In this study, miRNA expression profiles were determined in clear cell renal cell carcinomas (ccRCC) and in matched normal kidney tissues by using a miRNA microarray platform which covers a total of 851 human miRNAs. Differential expression of 74 miRNAs were identified between ccRCC specimens and their matched adjacent noncancerous tissues, of which 30 were significantly upregulated in ccRCCs, and the other 44 were downregulated (fold change ≥ 2, P < 0.05). Interestingly, miR-200c was commonly downregulated in ccRCC specimens and ccRCC cell lines with significant functional consequences. Growth curve and FACS assay indicated that overexpression of miR-200c suppressed cell growth and induced cell-cycle arrest at G0-G1 phases in SN12-PM6 and 786-O cells. Furthermore, miR-200c could suppress in vivo tumor growth of SN12-PM6 cells in mice. Bioinformatics exposed cyclin-dependent kinase 2 (CDK2) as a potential target of miR-200c, which was validated using a luciferase reporter assay. Mechanistic investigations revealed that miR-200c was directly responsible for suppressing the expression of CDK2 in ccRCC cell lines and xenografts. Taken together, miR-200c plays an antioncogenic role in ccRCC, through controlling cell growth and cell-cycle progression by downregulating the G1-S regulator CDK2.
Implications:
miR-200c exerts its novel antioncogenic function in renal cell carcinoma by controlling CDK2-dependent cell growth and cell-cycle progression.
Insights
MicroRNA-200c (miR-200c) functions as a tumor suppressor in clear cell renal cell carcinoma (ccRCC). It inhibits cancer cell growth and progression by targeting cyclin-dependent kinase 2 (CDK2).
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) expression is altered in various cancers, but their precise roles remain unclear.
- Clear cell renal cell carcinoma (ccRCC) is a major cancer where miRNA functions require further elucidation.
Purpose of the Study:
- To investigate miRNA expression profiles in ccRCC.
- To determine the specific role and molecular mechanisms of miR-200c in ccRCC progression.
Main Methods:
- miRNA microarray analysis of ccRCC tissues and matched normal kidney tissues.
- Cell growth assays, FACS analysis, and in vivo tumor growth studies.
- Bioinformatics analysis, luciferase reporter assays, and Western blotting to identify and validate miR-200c targets.
Main Results:
- 74 differentially expressed miRNAs were identified in ccRCC, with 44 downregulated and 30 upregulated.
- miR-200c was significantly downregulated in ccRCC and suppressed cell growth and induced G0-G1 cell-cycle arrest.
- miR-200c suppressed in vivo tumor growth and its target, cyclin-dependent kinase 2 (CDK2), was validated.
Conclusions:
- miR-200c exhibits an antioncogenic role in ccRCC.
- miR-200c controls ccRCC cell growth and cell-cycle progression by downregulating CDK2.
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