MicroRNA-155 Is Regulated by the Transforming Growth Factor β/Smad Pathway and Contributes to Epithelial Cell Plasticity by Targeting RhoA

被引：561

作者：

Kong, William ^{[1
,4
]}

Yang, Hua ^{[1
]}

He, Lili ^{[1
]}

Zhao, Jian-jun ^{[1
]}

Coppola, Domenico ^{[2
]}

Dalton, William S. ^{[3
]}

Cheng, Jin Q. ^{[1
]}

机构：

[1] H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL 33612 USA

[2] H Lee Moffitt Canc Ctr & Res Inst, Dept Pathol, Tampa, FL 33612 USA

[3] H Lee Moffitt Canc Ctr & Res Inst, Dept Expt Therapeut, Tampa, FL 33612 USA

[4] Univ S Florida, Coll Med, Dept Pathol & Cell Biol, Tampa, FL 33612 USA

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2008年 / 28卷 / 22期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1128/MCB.00941-08

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：

Transforming growth factor beta (TGF-beta) signaling facilitates metastasis in advanced malignancy. While a number of protein-encoding genes are known to be involved in this process, information on the role of microRNAs (miRNAs)in TGF-beta-induced cell migration and invasion is still limited. By hybridizing a 515-miRNA oligonucleotide-based microarray library, a total of 28 miRNAs were found to be significantly deregulated in TGF-beta-treated normal murine mammary gland (NMuMG) epithelial cells but not Smad4 knockdown NMuMG cells. Among upregulated miRNAs, miR-155 was the most significantly elevated miRNA. TGF-beta induces miR-155 expression and promoter activity through Smad4. The knockdown of miR-155 suppressed TGF-beta-induced epithelial-mesenchymal transition (EMT) and tight junction dissolution, as well as cell migration and invasion. Further, the ectopic expression of miR-155 reduced RhoA protein and disrupted tight junction formation. Reintroducing RhoA cDNA without the 3' untranslated region largely reversed the phenotype induced by miR-155 and TGF-beta. In addition, elevated levels of miR-155 were frequently detected in invasive breast cancer tissues. These data suggest that miR-155 may play an important role in TGF-beta-induced EMT and cell migration and invasion by targeting RhoA and indicate that it is a potential therapeutic target for breast cancer intervention.

引用

页码：6773 / 6784

页数：12

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