Regulation of TGF-β2-induced epithelial–mesenchymal transition and autophagy in lens epithelial cells by the miR-492/NPM1 axis

TL;DR

This study explores how miR-492 and NPM1 regulate cell processes like autophagy and EMT in lens cells, offering new insights into cataract development and treatment.

Contribution

The study identifies a novel regulatory axis involving miR-492 and NPM1 in cataract-related cell processes.

Findings

NPM1 overexpression promotes cell proliferation and prevents apoptosis in lens epithelial cells.

miR-492 negatively regulates NPM1 and autophagy-related proteins in response to TGF-β2.

NPM1 knockdown restores autophagy suppressed by miR-492 mimics, suggesting a complex regulatory interaction.

Abstract

A cataract is a clinically common blinding disease closely related to the aging of the eye cells, which has become a major health killer in the elderly. Our research seeks to analyze the primary targets linked to the pathogenesis of cataracts during the aging process. We performed bioinformatics analyses on the GSE101727 dataset to discover genes linked with aging and cataracts. To explore the impacts of Nucleophosmin 1 (NPM1) on cell apoptosis, proliferation, as well as epithelial–mesenchymal transition (EMT) processes, in vitro tests, such as western blotting, flow cytometry, and MTT, were carried out. Additionally, the study incorporated transforming growth factor β2 (TGF-β2) to examine its function in cellular responses, chloroquine (CQ) to regulate autophagic flow, and H2O2 therapy to mimic oxidative stress. Our study discovered seven aging-related genes, including NPM1, that had substantial relationships with cataracts. NPM1 overexpression was shown to boost cell proliferation and prevent apoptosis in SRA01/04 cells. Notably, NPM1 modulated the TGF-β signaling pathway, influencing cell proliferation and EMT processes. miR-429 was shown to be adversely regulating NPM1 and autophagy-related proteins, as demonstrated by changes in their expression in response to TGF-β2 treatment. Furthermore, NPM1 knockdown restored autophagy activity suppressed by miR-429 mimics, indicating a complex interaction of miR-429, NPM1, and TGF-β2 pathways in regulating autophagy and EMT. Lens epithelial cell proliferation and apoptosis were largely regulated by NPM1, as well as autophagy and EMT, which were significantly mediated by TGF-β2 and the miR-429/NPM1 axis. These results implied new possible targets for prognosis and therapy of cataracts.

Figures