Reduced expression of CENP-E contributes to the development of hepatocellular carcinoma and is associated with adverse clinical features

Autor: Peirong He, Penghui Hu, Chaohao Yang, Xingxiang He, Ming Shao, Yiguang Lin
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Biomedicine & Pharmacotherapy, Vol 123, Iss , Pp 109795- (2020)
Druh dokumentu: article
ISSN: 0753-3322
DOI: 10.1016/j.biopha.2019.109795
Popis: Human kinesin centromere-associated protein E (CENP-E), one of spindle checkpoint proteins, has been identified as a tumor suppressor in several types of cancer, however, its role in hepatocarcinogenesis remains unknown. Here we investigated the role of CENP-E in human hepatocellular carcinoma (HCC) employing HCC cell lines (Hep3B, SMMC7721, and QGY7701), animal models, and patient’s clinical samples and data. We demonstrated that down-regulation of CENP-E by CENP-E-silencing shRNAs significantly promoted HCC proliferation/growth both in vitro and in vivo. Further studies found that CENP-E suppressed the proliferation of HCC cells by halting cell cycle progression at the G1-S phase and accelerating cell apoptosis. Analyses of HCC patient samples and clinical data revealed that CENP-E was significantly down-regulated in HCC tissues and low CENP-E expression was significantly associated with patient’s adverse clinicopathological features: poor prognosis, advanced TNM stage, metastasis, and larger tumor size. Multivariate analysis indicated that CENP-E was an independent prognostic factor predicting outcomes of advanced HCC patients. Our data suggest that loss of CENP-E contributes to HCC development and is strongly associated with adverse HCC clinical pathology. Thus, CENP-E could be a novel target for new treatments and a useful prognostic biomarker for HCC patients.
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