A proposed model of LCDR / hnRNP K / LAPTM 5-axis that promotes the etiology of lung cancer. Credit: Gao Shan
Chinese scientists recently reported a key role in tumor survival of long non-coding RNAs regulated by histone acetylation, called lysosomal cell death regulators (LCDRs), and potential diagnosis and treatment of lung cancer. Provide a target.
Researchers led by Professor Gao Shan of the Suzhou Biomedical Engineering Institute of the Chinese Academy of Sciences (CAS) have been knocked down by LCDR. lung cancer Cells can promote apoptosis. The results were published in PNAS..
Lysosomes are involved in cell homeostasis, and their dysregulation is associated with a variety of human diseases, including: cancer.. LncRNAs are non-coding RNAs longer than 200 nucleotides, and their dysregulation is associated with cancer features. They are DNA, RNA, and Protein aggregateIncludes the Heterogeneous Ribonucleic Acid Protein (hnRNP) family.
However, it is not known whether lncRNAs and / or hnRNPs are involved in lysosome-mediated cancer survival.
In this study, LCDRs regulate the stability of lysosomal-related protein transmembrane 5 (LAPTM5) transcripts that bind to the heterogeneous nucleoprotein K (hnRNP K) and maintain lysosomal membrane integrity.
According to researchers, knockdown of LCDR, hnRNP K, or LAPTM5 promoted lysosomal membrane permeabilization and lysosomal cell death, causing apoptosis. Overexpression of LAPTM5 or cathepsin B inhibitors partially restored the effect of this axis on lysosomal cell death in vitro and in vivo.
Similarly, targeting LCDR significantly reduced tumor growth in xenografts from patients with lung adenocarcinoma (LUAD), using systematic siRNA delivery via nanoparticles (NP). Caused significant cell death.
In addition, LCDR / hnRNP K / LAPTM5 were upregulated in LUAD tissue and their co-expression showed an increase in the diagnostic value of LUAD.
These findings shed light on LCDR / hnRNP K / LAPTM5 as potential therapeutic targets, demonstrating lysosome targeting as a promising strategy in the treatment of cancer.
LCDR Q: 0 regulates lysosomal membrane integrity by hnRNP K-stabilized transcripts and promotes cell survival. Minutes of the National Academy of Sciences (2022). DOI: 10.1073 / pnas.2110428119..
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