Pirin Promotes the Progression of Non-Small-Cell Lung Cancer by Increasing ODC1 to Suppress Autophagy

• Published in: Journal of proteome research 2024-05, Vol.23 (5), p.1713-1724
• Main Authors: Li, Yan-Ping, Huang, Zi-Jia, He, Quan-Kuo, Li, Yi-Xiang, Zhao, Xiang-Pei, Ma, Zhong-Qi, Qin, Mei-Jing, Chen, Ai-Wen, Wei, Qiu, Wang, Yang, Lu, Chun-Hua
• Format: Article
• Language: English
• Subjects: A549 Cells; Autophagy - genetics; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Proliferation - genetics; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Ornithine Decarboxylase - genetics; Ornithine Decarboxylase - metabolism; Prognosis; Up-Regulation
• ISSN: 1535-3893; 1535-3907
• DOI: 10.1021/acs.jproteome.3c00871

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.