Pan-cancer landscape of CENPO and its underlying mechanism in LUAD

作者全名："Shi, Tongdong; Hu, Zaoxiu; Tian, Li; Yang, Yanlong"

作者地址："[Yang, Yanlong] Kunming Med Univ, Dept Thorac Surg, Affiliated Hosp 1, 295 Xichang Rd, Kunming 650032, Yunnan, Peoples R China; [Tian, Li] Chongqing Med Univ, Dept Infect Dis, Key Lab Mol Biol Infect Dis, Affiliated Hosp 2, 74 Linjiang Rd, Chongqing 400010, Peoples R China; [Tian, Li] Chongqing Med Univ, Inst Viral Hepatitis, Affiliated Hosp 2, 74 Linjiang Rd, Chongqing 400010, Peoples R China; [Hu, Zaoxiu] Kunming Med Univ, Dept Pathol, Affiliated Hosp 3, 519 Kunzhou Rd, Kunming 650118, Yunnan, Peoples R China; [Shi, Tongdong] Chongqing Med Univ, Dept Infect Dis, Key Lab Mol Biol Infect Dis, Minist Educ,Affiliated Hosp 2, 288 Tianwen Ave, Chongqing 401336, Peoples R China"

通信作者："Yang, YL (通讯作者)，Kunming Med Univ, Dept Thorac Surg, Affiliated Hosp 1, 295 Xichang Rd, Kunming 650032, Yunnan, Peoples R China."

来源：RESPIRATORY RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000968727400002

JCR分区：Q1

影响因子：4.7

年份：2023

卷号：24

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Pan-cancer; CENPO; Immune infiltration; LUAD; Cell growth; mTOR signaling

摘要："BackgroundCentromere protein O (CENPO) is a newly discovered constitutive centromeric protein, associated with cell death. However, little is known about how CENPO expression is associated with human cancers or immune infiltration. Here, we assessed the function of CENPO in pan-cancer and further verified the results in lung adenocarcinoma (LUAD) through in vitro and in vivo experiments.MethodsSangerbox and TCGA databases were used to evaluate the CENPO expression level in different human cancer types. A subsequent evaluation of the potential role of CENPO as a diagnostic and prognostic biomarker in pancancer was conducted. The CENPO mutations were analyzed using the cBioPortal database and its function was analyzed using the LinkedOmics and CancerSEA databases. The TIMER2 and TISIDB websites were used to find out how CENPO affects immune infiltration. The expression level of CENPO in LUAD was revealed by TCGA database and immunohistochemical (IHC) staining. Targetscan, miRWalk, miRDB, miRabel, LncBase databases, and Cytoscape tool were used to identify microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) that regulate expression and construct ceRNA network. Subsequently, loss-of-function assays were performed to identify the functions of CENPO on the malignant behavior and tumor growth of LUAD in vitro and in vivo experiments.ResultsIn most cancers, CENPO was upregulated and mutated, which predicted a poorer prognosis. Furthermore, infiltration of CENPO and myeloid-derived suppressor cells (MDSC) showed a significant positive correlation, while T-cell NK infiltration showed a significant negative correlation in most cancers. CENPO was expressed at high levels in LUAD and was correlated with p-TNM stage. Furthermore, CENPO knockdown suppressed the malignant phenotypes of LUAD cells, manifested by slower proliferation, cycle in G2, increased apoptosis, decreased migration, and attenuated tumorigenesis. Furthermore, CENPO knockdown decreased CDK1/6, PIK3CA, and inhibited mTOR phosphorylation, suggesting that the mTOR signaling pathway may be involved in CENPO-mediated regulation of LUAD development.ConclusionsIn pan-cancer, especially LUAD, CENPO may be a potential biomarker and oncogene. Furthermore, CENPO has been implicated in immune cell infiltration in pan-cancer and represents a potential immunotherapeutic target for tumor therapy."

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