Tumor-suppressive microRNA-135a inhibits cancer cell proliferation by targeting the c-MYC oncogene in renal cell carcinoma
Yasutoshi Yamada
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
These authors contributed equally to this work.Search for more papers by this authorHideo Hidaka
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
These authors contributed equally to this work.Search for more papers by this authorNaohiko Seki
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan
Search for more papers by this authorHirofumi Yoshino
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Search for more papers by this authorTakeshi Yamasaki
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Search for more papers by this authorToshihiko Itesako
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Search for more papers by this authorMasayuki Nakagawa
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Search for more papers by this authorCorresponding Author
Hideki Enokida
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
To whom correspondence should be addressed.
E-mail: [email protected]
Search for more papers by this authorYasutoshi Yamada
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
These authors contributed equally to this work.Search for more papers by this authorHideo Hidaka
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
These authors contributed equally to this work.Search for more papers by this authorNaohiko Seki
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan
Search for more papers by this authorHirofumi Yoshino
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Search for more papers by this authorTakeshi Yamasaki
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Search for more papers by this authorToshihiko Itesako
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Search for more papers by this authorMasayuki Nakagawa
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Search for more papers by this authorCorresponding Author
Hideki Enokida
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
To whom correspondence should be addressed.
E-mail: [email protected]
Search for more papers by this authorAbstract
Recently, many studies have suggested that microRNAs (miRNAs) are involved in cancer cell development, invasion, and metastasis of various types of human cancers. In a previous study, miRNA expression signatures from renal cell carcinoma (RCC) revealed that expression of microRNA-135a (miR-135a) was significantly reduced in cancerous tissues. The aim of this study was to investigate the functional significance of miR-135a and to identify miR-135a-mediated molecular pathways in RCC cells. Restoration of mature miR-135a significantly inhibited cancer cell proliferation and induced G0/G1 arrest in the RCC cell lines caki2 and A498, suggesting that miR-135a functioned as a potential tumor suppressor. We then examined miR-135a-mediated molecular pathways using genome-wide gene expression analysis and in silico analysis. A total of 570 downregulated genes were identified in miR-135a transfected RCC cell lines. To investigate the biological significance of potential miR-135a-mediated pathways, we classified putative miR-135a-regulated genes according to the Kyoto Encyclopedia of Genes and Genomics pathway database. From our in silico analysis, 25 pathways, including the cell cycle, pathways in cancer, DNA replication, and focal adhesion, were significantly regulated by miR-135a in RCC cells. Moreover, based on the results of this analysis, we investigated whether miR-135a targeted the c-MYC gene in RCC. Gain-of-function and luciferase reporter assays showed that c-MYC was directly regulated by miR-135a in RCC cells. Furthermore, c-MYC expression was significantly upregulated in RCC clinical specimens. Our data suggest that elucidation of tumor-suppressive miR-135a-mediated molecular pathways could reveal potential therapeutic targets in RCC.
Supporting Information
| Filename | Description |
|---|---|
| cas12072-sup-0001-FigS1.tifimage/tif, 645.5 KB | Fig. S1. Cell viabilities altered in the miR-135a stable transfectant. |
| cas12072-sup-0002-TableS1.docWord document, 2.9 MB | Table S1. Down-regulated genes in miR-135a transfectants. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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