Let-7a-5p represses proliferation, migration, invasion and epithelial-mesenchymal transition by targeting Smad2 in TGF-β2-induced human lens epithelial cells

ABSTRACT

Transforming growth factor b2 (TGF-b2)/Smad signaling is widely accepted as a key inducer of proliferationand epithelial-mesenchymal transition (EMT) of human lens epithelial cells (LECs), contributing to thedevelopment of posterior capsule opacification (PCO). Increasing evidence shows that microRNAs (miRNAs)play important roles in PCO pathogenesis. Herein, we aimed to explore the role and molecular mechanism oflet-7a-5p on TGF-b2-induced proliferation and EMT in LECs. qRT-PCR was performed to detect theexpression of let-7a-5p and Smad2 mRNA. Western blot was used to determine the Smad2 level and theinduction of EMT. The targeted correlation between let-7a-5p and Smad2 was confirmed using dual-luciferasereporter and RNA immunoprecipitation assays. CCK-8 assay was employed to determine cell proliferation, andtranswell assays were performed to assess cell migration and invasion. We found that TGF-b2 induced EMT ofLECs, and TGF-b2 upregulated Smad2 expression and reduced let-7a-5p expression in LECs. Smad2 was adirect target of let-7a-5p. Moreover, let-7a-5p upregulation repressed proliferation, migration, invasion andEMT in TGF-b2-induced LECs. But, Smad2 expression restoration abrogated the inhibitory effect of let-7a-5pupregulation. In conclusion, our data indicated that let-7a-5p upregulation repressed TGF-b2-induced proliferation, migration, invasion and EMT at least partly by targeting Smad2 in LECs, highlighting that let-7a-5pmight act as a promising therapeutic target to intervene to the progression of PCO.