MiR-630 inhibits proliferation by targeting CDC7 kinase, but maintains the apoptotic balance by targeting multiple modulators in human lung cancer A549 cells

摘要: MicroRNAome analyses have shown microRNA-630 (miR-630) to be involved in the regulation of apoptosis. However, its apoptotic role is still debated and participation DNA replication unknown. Here, we demonstrate that miR-630 inhibits cell proliferation by targeting cell-cycle kinase 7 (CDC7) kinase, but maintains balance multiple activators apoptosis under genotoxic stress. We identified a novel regulatory mechanism CDC7 gene expression, which downregulated expression recognizing binding four sites 3'-UTR. found was highly expressed A549 NIH3T3 cells where downregulated, lower H1299, MCF7, MDA-MB-231, HeLa 2BS upregulated. Furthermore, induction occurred commonly variety human cancer immortalized response agents. Importantly, downregulation associated with cisplatin (CIS)-induced inhibitory cells. Mechanistically, exerted blocking CDC7-mediated initiation synthesis inducing G1 arrest, CIS exposure. On one hand, promoted CDC7; on other it reduced downregulating several modulators such as PARP3, DDIT4, EP300 downstream effector p53, thereby maintaining balance. Our data indicate has bimodal damage. also support notion certain mRNA can targeted miRNAs, particular an miRNA may target set mRNAs. These afford comprehensive view microRNA-dependent control