LncRNA HAR1A Suppresses the Development of Non-Small Cell Lung Cancer by Inactivating the STAT3 Pathway

Abstract

It is imperative to advance the understanding of lung cancer biology. The Cancer Genome Atlas (TCGA) dataset was used for bioinformatics analysis. CCK-8 assay, flow cytometry, and western blot were performed in vitro, followed by in vivo study. We found that lncRNA <i>Highly Accelerated Region 1A</i> (<i>HAR1A</i>) is significantly downregulated in lung adenocarcinoma (LUAD) and negatively associated with prognosis. We improved the prognostic accuracy of <i>HAR1A</i> in LUAD by combining genes regulating cell apoptosis and cell cycle to generate a 23-gene signature. Nomogram and decision curve analysis (DCA) confirmed that the gene signature performed robustly in predicting overall survival. Gene set variation analysis (GSVA) demonstrated several significantly upregulated malignancy-related events in the high-risk group, including DNA replication, DNA repair, glycolysis, hypoxia, MYC targets v2, and mTORC1. The risk signature distinguished LUAD patients suitable for chemotherapies or targeted therapies. Additionally, the knockdown of <i>HAR1A</i> accelerated NSCLC cell proliferation but inhibited apoptosis and vice versa. <i>HAR1A</i> regulated cellular activities through the STAT3 signaling pathway. The tumor-suppressing role of <i>HAR1A</i> was verified in the mouse model. Overall, the gene signature was robustly predictive of prognosis and sensitivity to anti-tumor drugs. <i>HAR1A</i> functions as a tumor suppressor in NSCLC by regulating the STAT3 signaling pathway.