KMID : 0624620090420110725
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BMB Reports 2009 Volume.42 No. 11 p.725 ~ p.730
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Down-regulation of the cyclin E1 oncogene expression by microRNA-16-1 induces cell cycle arrest in human cancer cells
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Wang Fu
Zhou Yu Zhang Yi Fu Xiang-Dong
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Abstract
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Cyclin E1 (CCNE1), a positive regulator of the cell cycle, controls the transition of cells from G1 to S phase. In numerous human tumors, however, CCNE1 expression is frequently dysregulated, while the mechanism leading to its dysregulation remains incompletely defined. Herein, we showed that CCNE1 expression was subject to post-transcriptional regulation by a microRNA miR-16-1. This was evident at protein level of CCNE1 as well as its mRNA level. Further evident by dual luciferase reporter assay revealed that two evolutionary conserved binding sites on 3¡¯ UTR of CCNE1 were the direct functional target sites. Moreover, we showed that miR-16-1 induced G0/G1 cell cycle arrest by targeting CCNE1 and siRNA against CCNE1 partially phenocopied miR-16-1-induced cell cycle phenotype whereas substantially rescued anti-miR-16-1- induced phenotype. Together, all these results demonstrate that miR-16-1 plays a vital role in modulating cellular process in human cancers and indicate the therapeutic potential of miR-16-1 in cancer therapy.
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KEYWORD
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Cancer therapy, CCNE1, Cell cycle arrest, miR-16-1, Post-transcriptional regulation
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