MicroRNA 17-92 Cluster Mediates ETS1 and ETS2-Dependent RAS-Oncogenic Transformation

被引：17

作者：

Kabbout, Mohamed ^{[1
,2
,3
]}

Dakhlallah, Duaa ^{[2
,4
]}

Sharma, Sudarshana ^{[1
,3
]}

Bronisz, Agnieszka ^{[1
,3
]}

Srinivasan, Ruchika ^{[1
,2
,3
]}

Piper, Melissa ^{[4
,5
]}

Marsh, Clay B. ^{[4
,5
]}

Ostrowski, Michael C. ^{[1
,3
]}

机构：

[1] Ohio State Univ, Coll Med, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA

[2] Ohio State Univ, Grad Program Mol Cellular & Dev Biol, Columbus, OH 43210 USA

[3] Ohio State Univ, Ctr Comprehens Canc, Solid Tumor Program, Columbus, OH 43210 USA

[4] Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA

[5] Ohio State Univ, Coll Med, Dept Internal Med, Div Pulm Allergy Crit Care & Sleep Med, Columbus, OH 43210 USA

来源：

PLOS ONE | 2014年 / 9卷 / 06期

基金：

美国国家卫生研究院;

关键词：

C-MYC; TRANSCRIPTION FACTORS; GENE-EXPRESSION; CELLULAR-TRANSFORMATION; MIR-17-92; CLUSTER; BREAST-CANCER; CELLS; SURVIVAL; FAMILY; PROLIFERATION;

D O I：

10.1371/journal.pone.0100693

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The ETS-family transcription factors Ets1 and Ets2 are evolutionarily conserved effectors of the RAS/ERK signaling pathway, but their function in Ras cellular transformation and biology remains unclear. Taking advantage of Ets1 and Ets2 mouse models to generate Ets1/Ets2 double knockout mouse embryonic fibroblasts, we demonstrate that deletion of both Ets1 and Ets2 was necessary to inhibit Hras(G12V) induced transformation both in vitro and in vivo. Hras(G12V) expression in mouse embryonic fibroblasts increased ETS1 and ETS2 expression and binding to cis-regulatory elements on the c-Myc proximal promoter, and consequently induced a robust increase in MYC expression. The expression of the oncogenic microRNA 17-92 cluster was increased in Hras(G12V) transformed cells, but was significantly reduced when ETS1 and ETS2 were absent. MYC and ETS1 or ETS2 collaborated to increase expression of the oncogenic microRNA 17-92 cluster in Hras(G12V) transformed cells. Enforced expression of exogenous MYC or microRNA 17-92 rescued Hras(G12V) transformation in Ets1/Ets2-null cells, revealing a direct function for MYC and microRNA 17-92 in ETS1/ETS2-dependent Hras(G12V) transformation.

引用

页数：9

共 40 条

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