Abstract
Ultraviolet B (UVB) irradiation could trigger DNA double-strand breaks (DDSBs) and senescence in lens epithelial cells (LECs), thus inducing age-related cortical cataract (ARCC) formation. Cell-cycle irreversible arrest induced by DDSBs depended on excessive activation of ataxia-telangiectasia mutated kinase (ATM). We studied the up-regulated circular RNA circMRE11A_013 (circMRE11A) in LECs of ARCC and SRA01/04 cell lines under UVB exposure. In vitro, knockdown of circMRE11A in SRA01/04 cell lines enhanced cell viability and cell cycle, while over-expression of circMRE11A exhibited an opposite trend. Additionally, circMRE11A could bind to UBX domain-containing protein 1 (UBXN1), which might enhance excessive activation of ATM and initiate ATM/p53/p21 signaling pathway causing LECs cell-cycle arrest and senescence. In vivo, recombinant adeno-associated virus vectors (rAAV-2) virions of circMRE11A (circMRE11A-AAV2) was injected to Institute of Cancer Research mouse vitreous cavity. The circMRE11A-AAV2 could express in mouse lens at 4 weeks. The LECs aging and opacity lens were observed at 8 weeks after the injection. Together, our findings reveal a previously unidentified role of circMRE11A interacting with UBXN1 in enhancing ATM activity and inhibiting LECs cell-cycle in ARCC formation. The findings might give us a better understanding of ARC pathology and provide a novel and more effective therapeutic approaches for ARC treatment.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
