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Cell Commun Signal. 2014 Oct 11;12:66. doi: 10.1186/s12964-014-0066-6.

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

Wu J1,2, Lv Q3,4, He J5, Zhang H6,7, Mei X8, Cui K9,10, Huang N11,12, Xie W13, Xu N14, Zhang Y15.

Author information

1
School of Life Sciences, Tsinghua University, Beijing, 100084, PR China. wyh0794@gmail.com.
2
Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. wyh0794@gmail.com.
3
School of Life Sciences, Tsinghua University, Beijing, 100084, PR China. lvtsing@gmail.com.
4
Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. lvtsing@gmail.com.
5
Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. jie.he2004@gmail.com.
6
School of Life Sciences, Tsinghua University, Beijing, 100084, PR China. 380847315@qq.com.
7
Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. 380847315@qq.com.
8
ENT Department, Peking University Shenzhen Hospital, Shenzhen, 518055, PR China. xueshuang_mei@163.com.
9
School of Life Sciences, Tsinghua University, Beijing, 100084, PR China. cui.kai1107@gmail.com.
10
Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. cui.kai1107@gmail.com.
11
School of Life Sciences, Tsinghua University, Beijing, 100084, PR China. huangnunu2781781@126.com.
12
Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. huangnunu2781781@126.com.
13
Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. xiewd@sz.tsinghua.edu.cn.
14
Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. xu.naihan@sz.tsinghua.edu.cn.
15
Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China. zhangyo@sz.tsinghua.edu.cn.

Abstract

BACKGROUND:

Accelerated 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.

RESULTS:

Overexpression 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.

CONCLUSIONS:

This study demonstrates that miR-188 exerts anticancer effects, via downregulation of multiple G1/S related cyclin/CDKs and Rb/E2F signaling pathway.

PMID:
25304455
PMCID:
PMC4200121
DOI:
10.1186/s12964-014-0066-6
[Indexed for MEDLINE]
Free PMC Article

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