Unveiling the role of microRNA-7 in linking TGF-β-Smad-mediated epithelial-mesenchymal transition with negative regulation of trophoblast invasion

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Jin-Chung ShihHsiu-Ni Kung

Abstract

Several pregnancy complications result from abnormal trophoblast invasion. The dichotomous effect of TGF-β on epithelial-mesenchymal transition (EMT) between trophoblast invasion and cancer progression remains unknown and a critical concern. We attenuated the expression of TGF-β type 1 receptor (coding by TGFBR1) with RNA interference in trophoblastic cells and significantly enhanced the trophoblastic invasion. Analysis of microRNA profiles in trophoblasts indicated microRNA-7 as a key molecule linking TGF-β with the negative regulation of trophoblast invasion. We then attenuated TGFBR1 and miR-7 transcription by transducing either short hairpin RNA targeting TGFBR1 or anti-miR-7-locked nucleonic acid, and we observed an up-regulation of EMT-related transcription factors (TFs) and their downstream effectors, causing a mesenchymal transition of trophoblasts. Conversely, overexpression of TGFBR1 or miR-7 led to the epithelial transition of trophoblasts. Our results showed that TGF-β-induced miR-7 expression negatively modulated the TGF-β-SMAD family member 2-mediated EMT pathway via targeting EMT-related TFs and down-regulating their mesenchymal markers. These findings possibly explain, at least in part, why TGF-β exerts an oppos...Continue Reading

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Citations

Aug 15, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yuanhui JiaHao Ying
Aug 28, 2020·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Sen HanZhihong Yang
May 28, 2020·International Journal of Molecular Sciences·Asghar AliQuinton A Winger
Jan 23, 2021·Trends in Endocrinology and Metabolism : TEM·Yan LiPeter C K Leung
Apr 18, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mei-Tsz SuPao-Lin Kuo

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