MicroRNA-188 suppresses G1/S transition by targeting multiple cyclin/CDK complexes

Cell Communication and Signaling

Research

Jie He¹  Naihan Xu¹  Weidong Xie¹  Yaou Zhang¹  Xueshuang Mei²  Kai Cui³  Jiangbin Wu³  Haoxiang Zhang³  Qing Lv³  Nunu Huang³ 

[1] Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, 518055, Shenzhen, PR, China;ENT Department, Peking University Shenzhen Hospital, 518055, Shenzhen, PR, China;School of Life Sciences, Tsinghua University, 100084, Beijing, PR, China;Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, 518055, Shenzhen, PR, China;

关键词: MiR-188;    Cell cycle;    G1/S transition;    CDK;    Cyclin;    Rb;    E2F;   

DOI  :  10.1186/s12964-014-0066-6

 received in 2014-06-20, accepted in 2014-09-30,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundAccelerated cell cycle progression is the common feature of most cancers. MiRNAs can act as oncogenes or tumor suppressors by directly modulating cell cycle machinery. It has been shown that miR-188 is upregulated in UVB-irradiated mouse skin and human nasopharyngeal carcinoma CNE cells under hypoxic stress. However, little is known about the function of miR-188 in cell proliferation and growth control.ResultsOverexpression of miR-188 inhibits cell proliferation, tumor colony formation and G1/S cell cycle transition in human nasopharyngeal carcinoma CNE cells. Using bioinformatics approach, we identify a series of genes regulating G1/S transition as putative miR-188 targets. MiR-188 inhibits both mRNA and protein expression of CCND1, CCND3, CCNE1, CCNA2, CDK4 and CDK2, suppresses Rb phosphorylation and downregulates E2F transcriptional activity. The expression level of miR-188 also inversely correlates with the expression of miR-188 targets in human nasopharyngeal carcinoma (NPC) tissues. Moreover, studies in xenograft mouse model reveal that miR-188 is capable of inhibiting tumor initiation and progression by suppressing target genes expression and Rb phosphorylation.ConclusionsThis study demonstrates that miR-188 exerts anticancer effects, via downregulation of multiple G1/S related cyclin/CDKs and Rb/E2F signaling pathway.

【 授权许可】

Unknown   
© Wu et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.