Integrated RNA expression and alternative polyadenylation analysis identified CPSF1‐CCDC137 oncogenic axis in lung adenocarcinoma

• Published in: Environmental toxicology Vol. 39; no. 4; pp. 2405 - 2416
• Main Authors: Xudong, Xiang, Heng, Li, Benchao, Chen, Wenjie, Chen, Bao, Lei, Gaofeng, Li
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.04.2024; Wiley Subscription Services, Inc
• Subjects: Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma of Lung - genetics; alternative polyadenylation (APA); Analysis; Animals; Cancer; CCDC137; Comparative analysis; Correlation; CPSF1; Deregulation; Gene expression; Genes; Genomes; lung adenocarcinoma (LUAD); Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lungs; Neoplasms; Nucleic acids; Pathogenesis; Phenotypes; Polyadenylation; Polyadenylation - genetics; Ribonucleic acid; RNA; Tumors; CPSF1; lung adenocarcinoma (LUAD); CCDC137; alternative polyadenylation (APA)
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.24105

This study aims to analyze the RNA expression and alternative polyadenylation (APA) events and identify APA tuned genes with prognostic significance in lung adenocarcinoma (LUAD). Genome‐wide RNA expression profile and APA events were acquired in LUAD cancer and normal samples in GSE197346. Comparative analysis screened common deregulated genes and transcripts. All 11 and 19 transcripts were up and down expressed and polyadenylated in cancer samples, respectively. Clinical analysis found eight genes with prognostic significance, such as coiled‐coil domain containing 137 (CCDC137). Role of CCDC137 in LUAD was first reported in this study. The cellular and animal experiments indicated that downregulated CCDC137 suppressed the malignant tumor phenotype and tumor growth in LUAD. Then, to identify APA regulators for elevated CCDC137, we analyzed the expression of 26 APA regulators in GSE197346 and The Cancer Genome Atlas (TCGA), and found 4 differential regulators: CPSF1, CELF2, NUDT21, and ELAVL1. At last, the correlation of eight genes with four differential APA regulators was analyzed, and CPSF1 showed a strong positive correlation with CCDC137. Based on the above results, we propose an oncogenic axis of CPSF1‐CCDC137 in LUAD. This study first constructed a polyadenylation tuned RNA expression map in LUAD, and the proposed oncogenic axis of CPSF1‐CCDC137 would shed light on the pathogenesis of LUAD.