Small Molecule Inhibitor of Myogenic microRNAs Leads to a Discovery of miR-221/222-myoD-myomiRs Regulatory Pathway

被引：39

作者：

Tan, Su-Bee ^{[1
,2
]}

Li, Jinbo ^{[1
]}

Chen, Xi ^{[2
]}

Zhang, Wenjie ^{[1
]}

Zhang, Dianmu ^{[2
]}

Zhang, Chenyu ^{[2
]}

Li, Donghai ^{[2
]}

Zhang, Yan ^{[1
]}

机构：

[1] Nanjing Univ, Sch Chem & Chem Engn, State Key Lab Analyt Chem Life Sci, Nanjing 210093, Jiangsu, Peoples R China

[2] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China

来源：

CHEMISTRY & BIOLOGY | 2014年 / 21卷 / 10期

基金：

中国国家自然科学基金;

关键词：

SKELETAL; EXPRESSION;

D O I：

10.1016/j.chembiol.2014.06.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Myogenic microRNAs (myomiRs) that are specifically expressed in cardiac and skeletal muscle are highly relevant to myogenic development and diseases. Discovery and elucidation of unknown myomiRs-involved regulatory pathways in muscle cells are important but challenging due to the lack of proper molecular tools. We report here a miR-221/222-myoD myomiRs regulatory pathway revealed by using a small-molecule probe that selectively inhibits myomiRs including miR-1 miR-133a and miR-206. The small-molecule inhibitor screened from luciferase assay systems was found to inhibit myomiRs and differentiation of C2C12 cells. Using the small molecule as a probe we found that the transcriptional factor myoD which is upstream of myomiRs was further regulated by miR-221/222. This miR221/222-myoD-myomiRs regulatory pathway was confirmed by over-expressing or knockdown miR221/222 in muscle cells which respectively led to the inhibition or enhancement of myoD protein expression and subsequent downregulation or upregulation of myomiR expression.

引用

页码：1265 / 1270

页数：6

共 30 条

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