A potential diagnostic and therapeutic target for lung cancer—LCDR

Chinese scientists recently reported the critical role of histone acetylation-regulated long noncoding RNAs, called lysosome cell death regulators (LCDRs), in tumor survival, providing insights into the diagnosis and treatment of lung cancer.
a potential target
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Led by Prof.
GAO Shan from the Suzhou Institute of Biomedical Engineering Technology, Chinese Academy of Sciences, the scientists found that inhibiting LCDR in lung cancer cells can promote apoptosis
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Lysosomes are involved in cellular homeostasis and their dysregulation has been implicated in various human diseases including cancer
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However, whether lncRNAs and/or hnRNPs are involved in lysosome-mediated cancer survival has not been elucidated
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In the present study, LCDR binds heterogeneous nuclear ribonucleoprotein K (hnRNP K) to regulate the stability of lysosomal-associated protein transmembrane 5 (LAPTM5) transcripts, thereby maintaining lysosomal membrane integrity
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According to the researchers, downregulation of LCDR, hnRNP K or LAPTM5 promoted lysosomal membrane permeability and lysosomal cell death, leading to apoptosis
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Similarly, targeting LCDR significantly reduced tumor growth in lung adenocarcinoma patient xenografts (LUAD) and resulted in significant cell death via nanoparticle (NPs)-mediated systemic siRNA delivery

In addition, LCDR/hnRNP K/LAPTM5 was up-regulated in LUAD tissues, and their co-expression has a higher diagnostic value for LUAD

These findings reveal LCDR/hnRNP/K/LAPTM5 as a potential therapeutic target, and lysosome-targeted therapy is a promising cancer treatment strategy

Magazine

PNAS

LCDR Q:0 regulates the integrity of lysosomal membrane by hnRNP K–stabilized LAPTM5 transcript and promotes cell survival

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