Circ-MKLN1/miR-377-3p/CTGF Axis Regulates the TGF-β2-induced Posterior Capsular Opacification in SRA01/04 Cells

Curr Eye Res. 2022 Mar;47(3):372-381. doi: 10.1080/02713683.2021.1988983. Epub 2021 Dec 27.

Abstract

Objective: Posterior capsular opacification (PCO) is a common postoperative ocular complication after cataract surgery. Little research focused on the regulation of circular RNAs (circRNAs) in PCO. This study was designed to investigate the function of circRNA-muskelin (circ-MKLN1) in PCO.

Methods: SRA01/04 cells were treated with transforming growth factor (TGF)-β2. Cell viability was analyzed by Cell Counting Kit-8 (CCK-8) assay. Transwell assay was used for cell migration and invasion detection. Cell migration was also measured by wound healing assay. Epithelial-mesenchymal transition (EMT)-related proteins and connective tissue growth factor (CTGF) were quantified using western blot.

Results: Cell viability, migration, invasion and EMT process in SRA01/04 cells were facilitated by TGF-β2. Circ-MKLN1 expression was enhanced in 17 PCO lens samples relative to 19 normal lens samples and TGF-β2-treated SRA01/04 cells contrasted to control cells. Downregulation of circ-MKLN1 inhibited the effects of TGF-β2 on SRA01/04 cells. Circ-MKLN1 targeted miR-377-3p and the regulation of si-circ-MKLN1 for the TGF-β2-induced influences was related to the upregulation of miR-377-3p. CTGF was the target gene for miR-377-3p. CTGF knockdown also abolished the TGF-β2-mediated cell growth, migration and invasion of SRA01/04 cells. The function of miR-377-3p was achieved by reducing the CTGF level. TGF-β2-induced CTGF expression promotion was alleviated by si-circ-MKLN1 through upregulating the expression of miR-377-3p.

Conclusion: These results showed that circ-MKLN1 contributed to the progression of PCO in vitro by increasing the CTGF expression via sponging miR-377-3p. Circ-MKLN1 might be important for improving the molecular target therapy in PCO.

Keywords: CTGF; Circ-MKLN1; lens epithelial cells; miR-377-3p; posterior capsular opacification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capsule Opacification* / genetics
  • Capsule Opacification* / metabolism
  • Cell Adhesion Molecules / metabolism
  • Cell Proliferation
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism
  • Epithelial Cells / metabolism
  • Gene Expression Regulation
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / pharmacology
  • Lens, Crystalline* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / pharmacology
  • RNA, Circular / genetics
  • Transforming Growth Factor beta2 / pharmacology

Substances

  • Cell Adhesion Molecules
  • Intracellular Signaling Peptides and Proteins
  • MIRN377 microRNA, human
  • MKLN1 protein, human
  • MicroRNAs
  • RNA, Circular
  • Transforming Growth Factor beta2
  • Connective Tissue Growth Factor