miR-200c Prevents TGF-β1-Induced Epithelial-to-Mesenchymal Transition and Fibrogenesis in Mesothelial Cells by Targeting ZEB2 and Notch1

Abstract

Peritoneal fibrosis and loss of transport function is a common complication contributing to adverse outcomes in patients on long-term peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) in mesothelial cells is a salient feature, but its triggering mechanisms remain obscure. Dysregulation of microRNA (miR) expression is implicated in EMT and tissue fibrosis. We investigated the role of miR-200c in EMT and fibrogenesis in a murine PD model and in cultured peritoneal mesothelial cells. PD-fluid-treated mice showed peritoneal miR-200c expression reduced by 76.2% compared with PBStreated mice, and this was accompanied by increased peritoneal a-smooth muscle actin, fibronectin, and collagen expression. PD fluid and TGF-b1 both reduced miR-200c expression in cultured mesothelial cells, accompanied by downregulation of E-cadherin and decorin, and induction of fibronectin, collagen I and III, and transcription factors related to EMT. Decorin prevented the suppression of miR-200c by TGF-b1. Lentivirus-mediated miR-200c overexpression prevented the induction of fibronectin, collagen I, and collagen III by TGF-b1, independent of decorin, and partially prevented E-cadherin suppression by TGF-b1. Target genes of miR-200c were identified as ZEB2 and Notch1. Our data demonstrate that miR-200c regulates EMT and fibrogenesis in mesothelial cells, and loss of peritoneal miR-200c contributes to PD-associated peritoneal fibrosis.

LncRNA MAGI2-AS3 Is Regulated by BRD4 and Promotes Gastric Cancer Progression via Maintaining ZEB1 Overexpression by Sponging miR-141/200a

“…After examination of the transcript abundance of lncRNA MAGI2-AS3 by qPCR, we found that the RNAi experiments of MAGI2-AS3 in the HGC-27 cell line and the overexpression experiments of MAGI2-AS3 in the AGS cell line were successful (Figures 4C and 4D). The EMT process is an essential step for tumor cells to acquire metastasis 16 , 17 . Considering that MAGI2-AS3 is an EMT-related lncRNA, we further evaluated the effects of MAGI2-AS3 knockdown and overexpression on gastric cancer cell migration and cell invasion.…”

A Review on the Carcinogenic Roles of DSCAM-AS1

“…Another study in colorectal cancer cells has shown the sponging effect of DSCAM-AS1 on miR-137 ( Xu et al, 2020 ). This miRNA has been found to suppress expression of Notch-1, a protein with essential roles in cell proliferation and epithelial-mesenchymal transition (EMT) ( Chu et al, 2019 ). Suppression of DSCAM-AS1 expression in colorectal cancer cells has resulted in down-regulation of Notch-1 ( Xu et al, 2020 ).…”

Mechanisms of Peritoneal Mesothelial Cells in Peritoneal Adhesion

“…The peritoneum is covered by a thin layer of mesothelial cells [ 7 , 20 ]. Below the mesothelial cells, the basement membrane and interstitial subcutaneous tissue, including collagen fibers, blood vessels, and fibroblasts, are found [ 21 , 22 ]. PMCs have apical–basal polarity, intercellular junction complexes, and apical microvilli [ 23 ]; these structures may be the most basic form of PMCs that maintain peritoneal integrity.…”