Identification of an oncogenic role of centromere protein M in non-small cell lung cancer via CDC20/MYBL2/Wnt signals

Abstract Lung cancer is the most common carcinoma with high mortality. However, the underlying mechanism of pulmonary neoplasia and disease development remains poorly understood. Our study comprehensively analyzed the transcriptome profiles and clinical-pathological characteristics of 515 patients diagnosed with non-small cell lung cancer (NSCLC) retrieved from the TCGA database. We observed a significant upregulation of centromere protein M (CENPM) in tissues of NSCLC patients, which was positively correlated with adverse prognosis. Additionally, overexpression of CENPM significantly facilitated cell proliferation and enhanced tumorigenic potential of NSCLC cell lines (A549/NCI-H1299), resulting in accelerated tumor progression and shortened survival time in tumor-bearing mice. Mechanistically, CENPM activated the Wnt/β-catenin signaling pathway through cell division cycle 20 (CDC20)/ MYB proto-oncogene kike 2 (MYBL2) axis. Blockade of Wnt signaling or CDC20/MYBL2 axis suppressed the tumorigenic potential and proliferative characteristics-induced by CENPM. Our investigation highlighted an essential role of CENPM in promoting NSCLC development, and CENPM might represent a novel biomarker for predicting NSCLC progression in clinic.