The prognostic value and mechanisms of centromere protein M in patients with lung adenocarcinoma

Abstract

Background: Centromere protein M (CENPM) has been reported to exert important roles in promoting tumor initiation and progression. However, the expression, effect, impact on prognosis and underlying mechanism of CENPM in lung adenocarcinoma (LUAD) remain unclear. Methods: Seventy-eight paired clinical samples of LUAD and corresponding adjacent non-tumor (ANT) tissues were obtained. The clinical pathological data and clinical outcome were tested, including univariate and multivariate Cox regression model. The relationship between CENPM expression and LUAD prognosis were identified according to the data obtained from the Cancer Genome Atlas (TCGA) database. Then, we explored the protein and mRNA levels of CENPM in LUAD and paired ANT tissues, and analyzed the correlation between CENPM and LUAD overall survival in our patients. In vitro studies, LUAD cell lines were treated with CENPM-short hairpin RNA (shRNA) (shCENPM), or transfected with CENPM overexpression plasmids with or without LY294002 (PI3K inhibitor) treatment. Cell proliferation ability was determined through cell counting kit-8 (CCK-8) assays. Cell cycle and apoptosis were detected by flow cytometer. The migration and invasion ability were assessed through Transwell assay. In vivo studies, the growth of xenografts in nude mice were evaluated after shCENPM stimulated cells injection, and the proliferation and apoptosis of xenografts were also analyzed.Results: CENPM was significantly upregulated in LUAD patients compared with healthy controls, and CENPM upregulation was relevant to the higher pathological stages and poor survival rates in our LUAD patients. The bioinformatics analysis also revealed similar trends. CENPM could promote cell proliferation, cause alterations in cell cycle progression, enhance cell migration and invasion capacity, promote apoptosis in LUAD cell lines and promote the growth of xenografts in nude mice via regulation of AKT1/mTOR signaling pathway.Conclusions: CENPM was upregulated in LUAD patients, and it correlated with higher pathological stages and poor survival rates. CENPM could affect cell proliferation, cell cycle, cell migration and invasion capacity, and apoptosis in LUAD cell lines via regulation of AKT1/mTOR signaling pathway.