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MicroRNA-574-3p regulates epithelial mesenchymal transition and cisplatin resistance via targeting ZEB1 in human gastric carcinoma cells

Wang, Mingqi, Zhang, Renwen, Zhang, Shu, Xu, Rui, Yang, Qing
Gene 2019 v.700 pp. 110-119
cadherins, cell movement, cisplatin, drug resistance, epithelium, genes, human cell lines, humans, messenger RNA, metastasis, migratory behavior, neoplasm cells, protein content, stomach neoplasms, transcription factors, vimentin, zinc finger motif
MicroRNA-574-3p (miR-574-3p) has different roles in different cancer types. However, the exact regulation mechanism of miR-574-3p in gastric cancer (GC) progression remains unclear. Thus, we aimed to evaluate the role of miR-574-3p in GC metastasis. We investigated the mechanism via which miR-574-3p regulated cancer cell migration and invasion to determine the relationship between epithelial mesenchymal transition (EMT) and drug resistance. Our results indicated that human GC cell line SGC7901 cells were more sensitive to cisplatin (DDP), but SGC7901 cisplatin-resistant cells (SGC7901/DDP) were more resistant to DDP and had mesenchymal characteristics. In addition, miR-574-3p overexpression up-regulated E-cadherin expression, and concomitantly down-regulated the expression of vimentin. We also identified zinc finger E-box binding homeobox transcription factor 1 (ZEB1), a crucial EMT inducer gene, as a new target of miR-574-3p. In fact, miR-574-3p bound the 3′ untranslated region (3′-UTR) of ZEB1, regulating expression of this transcription factor at both the mRNA and protein levels. Furthermore, miR-574-3p overexpression reduced the migratory and invasive properties of the SGC7901/DDP cells and inhibited cisplatin (DDP) resistance in vitro and in vivo. In conclusion, the results indicated that miR-574-3p inhibited the EMT and enhanced cisplatin sensitivity in GC cells by suppressing ZEB1. These results provide further evidence for the critical roles of miR-574-3p and ZEB1 in invasion and migration regulation characteristics of GC cells.