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

Abstract

Many cases of blindness are caused by age-related cataracts (ARCs). N6-methyladenosine (m6A)-modified circRNA widely participates in disease progression. However, the role of m6A modification of circRNA in ARC is unclear. We mined and elucidated the functions and mechanisms of key circRNAs with m6A modification involved in ARC progression. The GSE153722 dataset was used to mine m6A-mediated key circRNA. Loss-of-function assays and rescue assays were used to explore the effect and mechanism of circRNA on ARC cell proliferation and apoptosis. Has_circ_0007905 was a hypermethylated and upregulated expression in the ARC group relative to the control group both in vivo and in vitro. Silencing of has_circ_0007905 promoted proliferation and inhibited the apoptosis of HLE-B3 cells. METTL3 was upregulated in HLE-B3 cells after ARC modeling and had four binding sites with has_circ_0007905 and a mediated m6A modification of has_circ_0007905. Proliferation was significantly inhibited and apoptosis of HLE-B3 cells was facilitated by METTL3 overexpression, whereas these effects were prevented by has_circ_0007905 silencing. Silencing of has_circ_0007905 led to an alteration in the transcriptome landscape. 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 silencing. Moreover, miR-6749-3p significantly decreased the luciferase activities of wild type plasmids with both of has_circ_0007905 and EIF4EBP1. MiR-6749-3p inhibitor blocked elevation in proliferation and reduced EIF4EBP1 expression and apoptosis conferred by has_circ_0007905 silencing. We reveal for the first time that the commitment of ARC progression is guided by METTL3/has_circ_0007905/miR-6749-3p/EIF4EBP1 axis, and the results provide new insights into ARC pathology.

N6-methyladenosine methylation analysis of circRNAs in acquired middle ear cholesteatoma

“…Specifically, among these 3,755 circRNAs, 3,742 exhibited hypermethylation while 13 showed hypomethylation ( Figure 1 ). Accumulating evidence has shown that aberrant m6A modification of circRNAs contribute to the development of various diseases, including hepatocellular carcinoma ( Chen et al, 2022 ), innate immune system inhibition ( Chen et al, 2019 ), osteosarcoma ( Liu et al, 2023 ) and age-related cataract progression ( Li et al, 2023 ). These suggest that the m6A-modification patterns of circRNA found in our study may play a significant role in the pathogenesis of middle ear cholesteatoma.…”

Paternal genetic effects of cadmium exposure during pregnancy on hormone synthesis disorders in ovarian granulosa cells of offspring

“…In addition, aberrant DNA methylation in imprinting control regions can also affect the expression of miRNAs associated with imprinting control regions [ 45 ]. Moreover, changes in transcription factors and m 6 A modifications may also play an important role in the regulation of miRNA expression [ 20 , 46 ]. Therefore, in this study, numerous altered miRNAs in the F2 and F3 generations may also be regulated by multiple mechanisms as described above.…”

Comparison of postoperative visual performance between trifocal intraocular lens and monofocal intraocular lens

“…C ataract is the first reversible blindness-causing eye disease worldwide; however, the underlying pathogenesis is yet inconclusive. Albeit age and some genetic factors 1,2 are the main causes of cataract formation. With the overall improvement in the social, economic, and medical development, the patients have put forward high requirements for the postoperative effect of cataract.…”