Chinese scientists recently reported the essential role of histone acetylation-regulated long noncoding RNA called as lysosome cell death regulator (LCDR) in tumor survival, supplying a potential diagnostic and restorative target for lung cancer.
Led by Prof. GAO Shan from the Suzhou Institute of Biomedical Engineering and Technology of the Chinese Academy of Sciences (CAS), these scientists revealed that knockdown of the LCDR in lung cancer cells might promote apoptosis. Results were published in PNAS.
Lysosome is involved in cellular homeostasis and its dysregulation has been connected to numerous human illness, including cancer. LncRNAs are noncoding RNAs with lengths longer than 200 nucleotides, whose dysregulation is associated with cancer hallmarks. They drive cancer development and survival by connecting with Protein, rna, and dna assemblies, consisting of the heterogeneous ribonucleic acid protein (hnRNP) family, which functions as alternative splicing, RNA stability, translation, and so on.
Lysosome is associated with cellular homeostasis and its dysregulation has been connected to numerous human illness, consisting of cancer. LncRNAs are noncoding RNAs with lengths longer than 200 nucleotides, whose dysregulation is related to cancer trademarks. They drive cancer growth and survival by connecting with Protein, dna, and rna assemblies, consisting of the heterogeneous ribonucleic acid protein (hnRNP) household, which works as alternative splicing, RNA stability, translation, and so on.
Whether lncRNAs and/or hnRNPs are involved in lysosome-mediated cancer survival has actually not been illuminated.
Proposed design for the LCDR/hnRNP K/LAPTM5 axis promoting the pathogenesis of lung cancer. Credit: GAO Shan
In this study, LCDR binds to heterogeneous nuclear ribonucleoprotein K (hnRNP K) to regulate the stability of lysosomal-associated protein transmembrane 5 (LAPTM5) transcript that maintains the integrity of the lysosomal membrane.
According to the researchers, knockdown of LCDR, hnRNP K or LAPTM5 promoted lysosomal membrane permeabilization and lysosomal cell death, therefore resulting in apoptosis. LAPTM5 overexpression or cathepsin B inhibitor partly brought back the effects of this axis on lysosomal cell death in vitro and in vivo.
Likewise, targeting LCDR substantially decreased tumor growth of patient-derived xenografts of lung adenocarcinoma (LUAD) and caused substantial cell death utilizing nanoparticles (NPs)- moderated systematic siRNA delivery.
Additionally, LCDR/hnRNP K/LAPTM5 were upregulated in LUAD tissues, and their co-expression revealed increased diagnostic value for LUAD.
These findings shed light on LCDR/hnRNP K/LAPTM5 as prospective restorative targets and lysosome targeting is an appealing strategy in cancer treatment.
Referral: “LCDR Q:0 regulates the stability of lysosomal membrane by hnRNP K– stabilized LAPTM5 records and promotes cell survival” 17 January 2022, Proceedings of the National Academy of Sciences.DOI: 10.1073/ pnas.2110428119.
This work was supported by the National Natural Science Foundation of China and the Strategic Pilot Science and Technology Project of CAS etc.
