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.
Keywords: Smad2; canonical pathway; microarray; placenta accreta; preeclampsia.