FUNDC1 Induces Apoptosis and Autophagy Under Oxidative Stress via PI3K/Akt/mTOR Pathway in Cataract Lens Cells

Abstract

Purpose The purpose of the study is to explore the mRNA and protein expression of FUNDC1 in cataract cells and tissues, and clarify the function and mechanism of FUNDC1 in cataract cells under oxidative stress. Methods We used bioinformatic analysis to screen differentially expressed genes in cataract cells from GSE153933. The expression of FUNDC1 in cataract specimens and cells was measured by reverse transcription quantitative polymerase chain reaction and western blotting. MethPrimer was used to predict CpG island of FUNDC1 promoter. The methylation of FUNDC1 in cataract specimens and cells was determined by methylation-specific polymerase chain reaction assay. Flow cytometry assay was used to measure cell apoptosis in FUNDC1-knockdown and -overexpression SRA01/04 cells. The expression of LC3 was analyzed by immunofluorescence assay. The expression of apoptosis-related proteins, autophagy, and PI3K/Akt/mTOR-related proteins was determined by western blotting. Results The results of bioinformatic analysis revealed that FUNDC1 was upregulated in cataract. FUNDC1 was high expression in SRA01/04 cells with H2O2 treatment, whereas hypomethylation of FUNDC1 in cataract lens cells under oxidative stress. The knockdown of FUNDC1 decreased cell apoptosis and autophagy in comparison with the negative control of SRA01/04 cells. While the overexpression of FUNDC1 elevated cell apoptosis and autophagy compared to the empty vector group in SRA01/04 cells. Mechanically, FUNDC1 reduced the phosphorylation of PI3K/Akt/mTOR pathway under oxidative stress in SRA01/04 cells. Conclusion Our study suggested that FUNDC1 deficiency restrains cell apoptosis and autophagy by inhibiting PI3K/Akt/mTOR signal pathway.