Curcumin Suppresses TGF-β2-Induced Proliferation, Migration, and Invasion in Lens Epithelial Cells by Targeting KCNQ1OT1/miR-377-3p/COL1A2 Axis in Posterior Capsule Opacification

Purpose: Posterior capsule opacification (PCO) is a common complication after cataract surgery, which can lead to secondary loss of vision. Curcumin has been reported to play a suppressive role in PCO progression, and the potential molecular mechanism was explored in this study. Methods: Cell viability and proliferation were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 5-Ethynyl-2’-deoxyuridine (EdU) assay. Transwell assay and wound healing assay were performed to assess cell invasion and migration abilities. Western blot assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were conducted to measure the expression of proteins and RNAs. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to confirm the interaction between microRNA-377-3p (miR-377-3p) and KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) or collagen type I alpha 2 chain (COL1A2). Results: Curcumin dose-dependently alleviated transforming growth factor-β2 (TGF-β2)-induced proliferation, migration, and invasion in SRA01/04 cells. KCNQ1OT1 was up-regulated in PCO patients and TGF-β2-induced SRA01/04 cells. Curcumin-induced protective effects in TGF-β2-induced SRA01/04 cells were largely overturned by KCNQ1OT1 overexpression. KCNQ1OT1 directly interacted with miR-377-3p and negatively regulated its expression. miR-377-3p silencing overturned Curcumin-mediated protective effects in SRA01/04 cells upon TGF-β2 treatment. miR-377-3p directly interacted with the 3’ untranslated region (3’UTR) of COL1A2. COL1A2 overexpression largely counteracted KCNQ1OT1 silencing-induced effects in TGF-β2-stimulated SRA01/04 cells. KCNQ1OT1 could up-regulate COL1A2 expression by sponging miR-377-3p in SRA01/04 cells. Conclusion: In conclusion, Curcumin suppressed TGF-β2-induced malignant changes in lens epithelial cells by targeting KCNQ1OT1/miR-377-3p/COL1A2 axis.