Direct repression of the oncogene CDK4 by the tumor suppressor miR-486-5p in non-small cell lung cancer
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Yang Shao1,*, Yu-Qing Shen1,*, Yan-Li Li1,*, Chen Liang1, Bing-Jie Zhang1, Sheng-Di Lu2, Yan-Yun He1,4, Ping Wang1, Qiang-Ling Sun3, You-Xin Jin1, Zhong-Liang Ma1
1School of Life Sciences, Shanghai University, Shanghai, China
2Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
3Central Laboratory, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
4Experimental Center for Life Sciences, Shanghai University, Shanghai, China
*These authors have contributed equally to this work
Qiang-Ling Sun, e-mail: firstname.lastname@example.org
You-Xin Jin, e-mail: email@example.com
Zhong-Liang Ma, e-mail: firstname.lastname@example.org
Keywords: miR-486-5p, CDK4, NSCLC, methylation, cell cycle
Received: October 11, 2015 Accepted: March 17, 2016 Published: March 31, 2016
MicroRNAs are a class of non-coding single-stranded RNA, 20-23 nucleotide in length, which can be involved in the regulation of gene expression. Through binding with 3’-untranslated regions (3’-UTR), microRNAs can cause degradation of target mRNAs or inhibition of translation, and thus regulating the expression of genes at the post-transcriptional level. In this study, we found that miR-486-5p was significantly downregulated in non-small cell lung cancer (NSCLC) tissues and cell lines, suggesting that miR-486-5p might function as a tumor suppressor in lung cancer. Additionally, we showed that CDK4, an oncogene that plays an important role in cell cycle G1/S phase progression, was directly targeted by miR-486-5p. Furthermore, our data reveals that knockdown of CDK4 by siRNA can inhibit cell proliferation, promote apoptosis, and impede cell-cycle progression. In epigenetics, the upstream promoter of miR-486-5p was strongly regulated by methylation in NSCLC. Collectively, our results suggest that miR-486-5p could not only inhibit NSCLC by downregulating the expression of CDK4, but also be as a promising and potent therapy in the near future.
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