Unveiling the role of microRNA-7 in linking TGF-β-Smad-mediated epithelial-mesenchymal transition with negative regulation of trophoblast invasion
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Journal Volume
33
Journal Issue
5
Pages
6281
Date Issued
2019-05
Author(s)
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 opposite effect on EMT during trophoblast invasion and cancer progression.-Shih, J.-C., Lin, H.-H., Hsiao, A.-C., Su, Y.-T., Tsai, S., Chien, C.-L., Kung, H.-N. Unveiling the role of microRNA-7 in linking TGF-β-Smad-mediated epithelial-mesenchymal transition with negative regulation of trophoblast invasion.
Subjects
Smad2; canonical pathway; microarray; placenta accreta; preeclampsia
Other Subjects
gelatinase B; locked nucleic acid; messenger RNA; microRNA; microRNA 7; nerve cell adhesion molecule; short hairpin RNA; Smad2 protein; Smad3 protein; transcription factor Slug; transcription factor Snail; transcription factor Twist; transforming growth factor beta receptor 1; transforming growth factor beta1; unclassified drug; uvomorulin; vascular endothelial cadherin; vimentin; microRNA; MIRN7 microRNA, human; Smad protein; TGFBR1 protein, human; transforming growth factor beta; Article; cancer cell; cell invasion; controlled study; down regulation; epithelial mesenchymal transition; female; gene function; gene overexpression; gene repression; gene silencing; gene targeting; HTR-8/SVneo cell line; human; human cell; mRNA expression level; placenta accreta; placenta previa; preeclampsia; priority journal; protein expression level; protein microarray; regulatory mechanism; RNA interference; TGF beta signaling; transactivation; trophoblast; upregulation; carcinogenesis; cell motion; genetics; HEK293 cell line; metabolism; pathology; physiology; trophoblast; Carcinogenesis; Cell Movement; Epithelial-Mesenchymal Transition; HEK293 Cells; Humans; MicroRNAs; Receptor, Transforming Growth Factor-beta Type I; Smad Proteins; Transforming Growth Factor beta; Trophoblasts
Publisher
FEDERATION AMER SOC EXP BIOL
Type
journal article