Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest

miR-34a 下调 CCND1 和 CDK6 导致细胞周期停滞

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作者:Fang Sun, Hanjiang Fu, Qin Liu, Yi Tie, Jie Zhu, Ruiyun Xing, Zhixian Sun, Xiaofei Zheng

Abstract

miRNAs regulate gene expression by inhibiting translation or by targeting messenger RNA (mRNA) for degradation in a post-transcriptional fashion. In the present study, we show that ectopic expression of miR-34a reduces both mRNA and protein levels of cyclin D1 (CCND1) and cyclin-dependent kinase 6 (CDK6). We also demonstrate that miR-34a targets the 3'-untranslated mRNA region of CCND1 as well as CDK6, which in turn interferes with phosphorylation of retinoblastoma. In addition, we show that overexpression of miR-34a induces a significant G1 cell-cycle arrest in the A549 cell line. Taken together, our data suggest that the effects of miR-34a on G1 cell cycle arrest are through the down-regulation of CCND1 and CDK6, which is associated with other targets of miR-34a either additively or synergistically.

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