METTL3-mediated m6A modification of has_circ_0007905 promotes age-related cataract progression through miR-6749-3p/EIF4EBP1

Age-related cataract (ARC) contributes many cases of blindness. N6-methyladenosine (m6A) modified circRNA are widely participated in disease progression. However, the role of m6A modification of circRNA in ARC has not been reported yet. We aimed to mine and elucidate functions and mechanisms of key circRNAs with m6A modification involved in ARC progression.Methods: GSE153722 dataset was used to mine m6A mediated key circRNA, and loss-of-function assays and rescue assays were used to explore the effect and mechanism of circRNA on ARC cell proliferation and apoptosis.Result: Has_circ_0007905 was hypermethylated and up-regulated expression in ARC group relative to control group both in vivo and in vitro. Silencing of has_circ_0007905 promoted proliferation and inhibited apoptosis of HLE-B3 cells. METTL3 have four binding sites with has_circ_0007905 and mediated m6A modification of has_circ_0007905. METTL3 was up-regulated in HLE-B3 cells after ARC modeling. METTL3 knockdown significantly facilitated proliferation and inhibited apoptosis of HLE-B3 cells, whereas these effects were prevented by has_circ_0007905 silencing. Silencing of has_circ_0007905 led to an alteration in transcriptome and differentially expressed genes were mainly involved in immune-related processes and pathways. EIF4EBP1 overexpression promoted apoptosis and suppressed proliferation, and also significantly reversed effects of has_circ_0007905. Moreover, miR-6749-3p significantly decreased the luciferase activities of wild type plasmid both of has_circ_0007905 and EIF4EBP1. MiR-6749-3p inhibitor blocked elevation in proliferation and reduction in EIF4EBP1 expression and apoptosis conferred by has_circ_0007905 silencing.Conclusion: We reveal for the first time that METTL3/has_circ_0007905/miR-6749-3p/EIF4EBP1 axis guide commitment of ARC progression and provide new insights into pathology of ARC.