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

By W. Kong, Huan Yang, Lili He, Jian-jun Zhao, D. Coppola, W. Dalton, J. Cheng. Molecular and Cellular Biology, 2008

724 citations recorded by the source corpus.

ABSTRACT Transforming growth factor β (TGF-β) 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-β-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-β-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-β induces miR-155 expression and promoter activity through Smad4. The knockdown of miR-155 suppressed TGF-β-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-β. 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-β-induced EMT and cell migration and invasion by targeting RhoA and indicate that it is a potential therapeutic target for breast cancer intervention.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c789ab46bf6a300002a1a4ea8b0398a2adc5ff87

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In Cancer Research

1. David A. Baker
2. Y. Hao
3. P. ten Dijke
4. R. Derynck
5. Samy Lamouille
6. Y. Fouad
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In Molecular Biology

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4. Yoko Katsuno
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6. Anurag Singh
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8. Y. Hao

Citations in the corpus

• Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties (2009, neutral): “For example, the increase in the oncogenic miR-155, which was recently reported to target and reduce the level of RHOA (Kong et al., 2008), may counteract the miR-122 effect.”
• TGF-&bgr; signaling and epithelial–mesenchymal transition in cancer progression (2013, background): “Accordingly, downregulation of miR-155 expression inhibits TGF-b-induced EMT [32].”
• TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis (2019, positive): “This change reduces RHOA protein and disrupts tight junction formation, leading to EMT [116].”
• MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. (2010, background): “Of note, miR-155 promotes pancreatic tumor development and mammary gland epithelial cell migration and invasion by targeting the tumor suppressors TP53INP1 and RhoA, respectively (8, 14).”
• A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. (2010, background): “Cell Stem Cell, Volume 7 Supplemental Information A Mesenchymal-to-Epithelial Transition Initiates and Is Required for the Nuclear Reprogramming of Mouse Fibroblasts Ronghui Li, Jialiang Liang, Su Ni, Ting Zhou, Xiaobing Qing, Huapeng Li, Wenzhi He, Jiekai Chen, Feng Li, Qiang Zhuang, Baoming Qin, J”
• EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer (2010, background): “Thus, mir-155 regulates epithelial plasticity by targeting RhoA and promoting TGF-b induced EMT as a result of the dissolution of tight junctions (Kong et al., 2008).”