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. 2022 May;47(5):735-746.
doi: 10.1080/02713683.2022.2053724. Epub 2022 Apr 7.

Interfering Hsa_circRNA_0060640 Suppresses TGF-β2-Induced Proliferation, Motility and EMT in Human Lens Epithelium Cells by Targeting miR-214-3p and Collagen Type I alpha2 Chain

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Interfering Hsa_circRNA_0060640 Suppresses TGF-β2-Induced Proliferation, Motility and EMT in Human Lens Epithelium Cells by Targeting miR-214-3p and Collagen Type I alpha2 Chain

Ming Guo et al. Curr Eye Res. 2022 May.

Abstract

Background: Circular RNA (circRNA) is a novel star factor in the research of ocular diseases including cataract and the most common postoperative complication posterior capsule opacification (PCO). Hsa_circRNA_0060640 (circ_0060640) is an age-related cataract-related circRNA. However, its role in cataractogenesis is unrevealed yet.

Methods: PCO in vitro model was established in human lens epithelium cells (hLECs) induced by transforming growth factor-beta2 (TGF-β2). RNA and protein expressions were respectively detected by quantitative PCR and western blotting. Direct interaction between two RNAs was predicted by Starbase tool and confirmed by dual-luciferase reporter assay. MTS and EdU assays measured cell proliferation; Transwell, starch wound and western blotting assays evaluated cell motility and epithelial-mesenchymal transition (EMT).

Results: Circ_0060640 expression is higher in anterior lens capsule tissues from human cataractous eyes and TGF-β2-stimulated hLECs cells line SRA01/04. RNA interference of circ_0060640 could prevent SRA01/04 cells from TGF-β2-induced cell proliferation, migration and invasion, accompanied with decreased N-cadherin and α-smooth muscle actin and increased E-cadherin. Mechanistically, circ_0060640 directly controls microRNA (miR)-214-3p expression and then regulates gene expression of collagen type I alpha2 chain (COL1A2). Notably, COL1A2 inhibition is underlying the protective role of circ_0060640 silencing and miR-214-3p ectopic expression in TGF-β2-stimulated SRA01/04 cells.

Conclusion: Circ_0060640 is a novel cataract-related gene and its silencing could block TGF-β2-evoked hLECs proliferation, motility and EMT in vitro via targeting miR-214-3p-COL1A2 axis. Therefore, targeting circ_0060640 via RNA interference might be a treatment strategy for PCO development.

Keywords: COL1A2; Circ_0060640; TGF-β2; human lens epithelium; miR-214-3p.

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