Open AccessLCDR regulates the integrity of lysosomal membrane by hnRNP K–stabilized LAPTM5 transcript and promotes cell survival
Author(s) -
Xiwang Yang,
Ya Wen,
Shaomin Liu,
Liqiang Duan,
Tongfeng Liu,
Zhou Tong,
Zhuo Wang,
Yinmin Gu,
Yi-Bo Xi,
Xiaodong Wang,
Dingsan Luo,
Ruobing Zhang,
Yajuan Liu,
Yan Wang,
Tianyou Cheng,
Siyuan Jiang,
Xiaofeng Zhu,
Xiaohui Yang,
Yongbo Pan,
Shuwen Cheng,
Qig Ye,
Jinfei Chen,
Xiaoding Xu,
Shan Gao
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2110428119
Subject(s) - microbiology and biotechnology , programmed cell death , biology , lysosome , heterogeneous nuclear ribonucleoprotein , apoptosis , transmembrane protein , cell growth , cell , rna interference , ribonucleoprotein , rna , cancer research , biochemistry , receptor , gene , enzyme
Significance Here, we report that the long noncoding RNAlysosome cell death regulator (LCDR ) mediates the survival of cancer cells, counteracting the effects of apoptosis triggered by lysosomal cell death pathways. Mechanistically,LCDR , as a cofactor for heterogenous nuclear ribonucleoprotein K (hnRNP K) to potentiate the stabilization of lysosomal membrane protein lysosomal-associated protein transmembrane 5 (LAPTM5), prevents lysosomal membrane permeabilization and promotes cancer cell survival. Clinically,LCDR , hnRNP K, and LAPTM5 are significantly up-regulated in lung adenocarcinoma (LUAD) patients. TargetingLCDR via nanoparticles-mediated RNA interference technology increases cell death in vitro and inhibits the growth of patient-derived xenografts of LUAD in vivo. Our study demonstrates thatLCDR contributes to cancer pathology by regulatingLCDR -mediated apoptosis.