lncRNA TUG1 regulates Smac/DIABLO expression by competitively inhibiting miR-29b and modulates the apoptosis of lens epithelial cells in age-related cataracts  

作　　者：Miaomiao Sun Ke Li Xiao Li Huajun Wang Li Li Guangying Zheng 

机构地区：[1]Department of Ophthalmology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450000,China [2]Department of Ophthalmology,Luohe City Central Hospital,Luohe,Henan 462000,China

出　　处：《Chinese Medical Journal》2023年第19期2340-2350,共11页中华医学杂志（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(Nos.81970786,81670836,and 82000875);the Natural Science Foundation of Henan Province,China(No.202300410397)

摘　　要：Background:As one of the early discovered long non-coding RNAs(lncRNA),taurine upregulation gene 1(TUG1)has been widely expressed in a variety of tumors.Moreover,it promotes cell proliferation,differentiation,apoptosis,and migration.However,our understanding of its importance in the pathogenesis of cataracts remains limited.This study aimed to explore the mechanism by which lncRNA TUG1 mediates lens epithelial cell apoptosis in age-related cataracts(ARC)by regulating the microRNAs(miR-29b)/second mitochondria-derived activator of caspases axis,and to identify more non-surgical strategies for cataract treatment.Methods:The messenger RNA expression levels of TUG1,miR-29b,and Smac were detected using quantitative real-time polymerase chain reaction in vivo and in vitro.The expression of the Smac protein was analyzed by Western blotting and immunofluorescence.Flow cytometry and cell counting kit-8 assays were used to detect the cell apoptosis and proliferation rates,respectively.The targeted regulatory relationship between lncRNA TUG1,miR-29b,and Smac was verified by viral vector construction,co-transfection,nuclear and cytoplasmic separation,luciferase reporter assays,and RNA immunoprecipitation.Results:TUG1 and Smac were expressed at high levels in ARC and HLE-B3 cells treated with 200μmol/L H_(2)O_(2),whereas miR-29b expression was decreased.In vitro cell experiments confirmed that down-regulation of TUG1 could inhibit the apoptosis of lens epithelial cells.Mechanistically,Smac expression was negatively regulated by miR-29b.TUG1 competitively inhibited miR-29b expression and caused greater release of Smac.In addition,miR-29b partially reversed the effects of TUG1 on human lens epithelial cell line cells.Conclusions:lncRNA TUG1 increases Smac expression and promotes apoptosis of lens epithelial cells in ARC by competitively inhibiting miR-29b.This mechanism is the cytological basis for ARC formation.Based on these results,the lncRNA TUG1/miR29b/Smac axis may be a new molecular pathway that regulates ARC developmen

关 键 词：APOPTOSIS CATARACT lncRNA TUG1 MicroRNA-29 SMAC 

分 类 号：R776.1[医药卫生—眼科]