LNCAROD was stabilized through N6-methyladenosine methylation and exerted its anticancer effects in lung squamous cell carcinoma by inhibiting SIRT1 activity via CCAR2.

Abstract

Background: Lung squamous cell carcinoma (LUSC), a deadly malignant tumor, is highly prevalent worldwide. Accumulating evidence indicates that long-chain noncoding RNAs play crucial regulatory roles in the occurrence and progression of LUSC. LNCAROD regulates the proliferation, migration, and invasion of cells by upregulating SERPINE1 expression in lung adenocarcinoma (LUAD). However, the functional mechanism of LNCAROD action in LUSC remains unclear. The aim of this study was to investigate the regulatory function and mechanism of LNCAROD action in the development of LUSC.

Methods: Using quantitative polymerase chain reaction (qPCR) detection, we determined the expression of LNCAROD in LUSC tissues and cell lines. Cell Counting Kit-8 (CCK-8), EdU (5-ethynyl-2'-deoxyuridine), JC-1 mitochondrial membrane potential, flow cytometry, colony formation, scratch healing, and Transwell assays were conducted, and cell proliferation, migration, and invasion, as well as physiological changes were assessed. The tumorigenicity of LUSC cells was analyzed by in vitro tumor formation in nude mice. Molecular interactions were verified via Western blotting, RNA-protein pull-down assay, RNA binding protein immunoprecipitation (RIP), N6-methyladenosine (m6A)-RIP, and coimmunoprecipitation (Co-IP) analyses.

Results: LNCAROD was specifically and highly expressed in LUSC cells and tissues. LNCAROD expression was mediated by IGF2BP2 m6A methylation, which, along with CCAR2, inhibited SIRTI1's acetylation activity. This further induced p53 protein acetylation and promoted the mitochondrial apoptosis of LUSC cells, thereby inhibiting cell proliferation, migration, and invasion.

Conclusions: LNCAROD is specifically highly expressed in LUSC cells and tissues and may be a tumor-suppressor gene. The findings contribute to a deeper understanding of the function of LNCAROD in LUSC, and it may serve as a potential prognostic marker for personalized medical diagnosis in clinical practice.