The Role And Molecular Mechanism Of Long Non-coding RNA LCDR In Lung Adenocarcinoma

Histone acetylation is an important regulation of epigenetic modification,which regulates gene expression and contributes to the initiation and progression of tumors.Long noncoding RNAs(lncRNAs)have been shown to play important roles in the initiation,progression and metastasis of tumors.Therefore,this study aims to explore histone acetylation regulated(HAR)lncRNAs,as well as its consequent molecular function and mechanism in lung cancer.Firstly,lncRNA expression profiles that are potentially regulated by histone acetylation are comprehensively constructed based on TSA-treated lung cells.To further identify commonly HAR lncRNAs that are deregulated in cancer,we analysized the clinical data of cancer patients from The Cancer Genome Atlas(TCGA),and reveal a role for a HAR lncRNA termed as lysosome cell death regulator(LCDR)in lung cancer cell survival,knockdown of which promotes apoptosis.Mechanistically,LCDR binds to heterogenous nuclear ribonucleoprotein K(hnRNP K)to regulate the stability of lysosomal-associated protein transmembrane 5(LAPTM5)transcript that maintains integrity of lysosomal membrane.Consequently,knockdown of LCDR,hnRNP K or LAPTM5 promotes lysosomal membrane permeabilization and lysosomal cell death,thus consequently resulting in apoptosis.LAPTM5 overexpression partially restores the effects of this axis on lysosomal cell death.Clinically,LCDR/hnRNP K/LAPTM5 are upregulated in lung cancer tissues and coexpression of this axis shows the increased diagnostic value for lung cancer.These findings shed light on LCDR/hnRNP K/LAPTM5 as potential therapeutic targets and targeting lysosome is a promising strategy in cancer treatment.