miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer

被引：330

作者：

Giannakakis, Antonis ^{[4
]}

Sandaltzopoulos, Raphael ^{[4
]}

Greshock, Joel ^{[2
]}

Liang, Shun

Huang, Jia ^{[2
]}

Hasegawa, Kosei

Li, Chunsheng

O'Brien-Jenkins, Ann

Katsaros, Dionyssios ^{[3
]}

Weber, Barbara L. ^{[2
]}

Simon, Celeste ^{[2
]}

Coukos, George ^{[2
]}

Zhang, Lin ^{[1
]}

机构：

[1] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA

[2] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

[3] Univ Turin, Dept Obstet & Gynecol, Turin, Italy

[4] Democritus Univ Thrace, Dept Mol Biol & Genet, Lab Gene Express Mol Diagnost & Modern Therapeut, Alexandroupolis, Greece

来源：

CANCER BIOLOGY & THERAPY | 2008年 / 7卷 / 02期

关键词：

microRNA; hypoxia; ovarian cancer;

D O I：

10.4161/cbt.7.2.5297

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

cancer pathogenesis. We studied miRNA genes that are regulated by hypoxia in ovarian cancer cell lines by TaqMan miRNA assay containing 157 mature miRNAs. MiR-210 was the most prominent miRNA consistently stimulated under hypoxic conditions. We provide evidence for the involvement of the HIF signaling pathway in miR-210 regulation. Biocomputational analysis and in vitro assays demonstrated that e2f transcription factor 3 (e2f3), a key protein in cell cycle, is regulated by miR-210. E2F3 was further confirmed to be downregulated at the protein level upon induction of miR-210. Importantly, we found remarkably high frequency of miR-210 gene copy deletions in ovarian cancer patients (64%, n = 114) and that gene copy number correlates with miR-210 expression levels. Taken together, our results indicate that miR-210 plays a crucial role in tumor onset as a key regulator of the hypoxia response and provide evidence for a link between hypoxia and the regulation of cell cycle.

引用

页码：255 / 264

页数：10

共 61 条

[1] The functions of animal microRNAs [J].