LCDR regulates the integrity of lysosomal membrane by hnRNP K–stabilized LAPTM5 transcript and promotes cell survival

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.