lncRNA LINC00960 promotes apoptosis by sponging ubiquitin ligase Nrdp1-targeting miR-183-5p  

作　　者：Hao Yang Tianxia Jiang Libin Fan Xiaobo Qiu 

机构地区：[1]College of Life Sciences,Anhui Medical University,Hefei 230032,China [2]Key Laboratory of Cell Proliferation and Regulation Biology,Ministry of Education,and College of Life Sciences,Beijing Normal University,Beijing 100875,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第1期91-102,共12页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Key R&D Program of China(No.2019YFA0802100);the National Natural Science Foundation of China(31530014);the Ministry of Science and Technology of China(No.2018YFC1003300);the Beijing Municipal Natural Science Foundation(No.217100029).

摘　　要：The ubiquitin ligase Nrdp1/RNF41 promotes the ubiquitin-dependent degradation of multiple important substrates,including BRUCE/BIRC6,a giant ubiquitin-conjugating enzyme inhibiting both apoptosis and autophagy.miR-183-5p is associated with various malignancies potentially by targeting dozens of genes.Here,we show that the lncRNA LINC00960 binds to the Nrdp1-targeting miR-183-5p and promotes apoptosis.Compared to other known miR-183-5p targets,Nrdp1 mRNA is among the few with top scores to complement miR-183-5p.miR-183-5p binds to the 3′UTR of Nrdp1 mRNA and downregulates Nrdp1 at both the mRNA and protein levels.The miR-183-5p mimics inhibit DNA damage-induced apoptosis probably by upregulating BRUCE level,whereas the miR-183-5p inhibitor suppresses the effects of miR-183-5p.LINC00960 is the noncoding RNA with the highest score to complement miR-183-5p.LINC00960 overexpression reduces,but its knockdown increases,the level of miR-183-5p,whereas LINC00960 overexpression increases,but its knockdown decreases,the level of Nrdp1 and apoptosis.Importantly,the expression of LINC00960,which is associated with multiple types of tumors,positively correlates with that of Nrdp1 in several tumors but inversely correlates with that of miR-183-5p in multiple human tumor cell lines,as analysed by quantitative PCR.Thus,miR-183-5p downregulates Nrdp1 expression and inhibits apoptosis,whereas LINC00960 upregulates Nrdp1 and promotes apoptosis by inhibiting miR-183-5p.These results may provide new ideas for the prevention,diagnosis and treatment of apoptosis-related diseases,such as tumors and neurodegenerative diseases.

关 键 词：Nrdp1 BRUCE APOPTOSIS lncRNA MIRNA 

分 类 号：R363[医药卫生—病理学]