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CBX1 Indicates Poor Outcomes and Exerts Oncogenic Activity in Hepatocellular Carcinoma.

Abstract：

:Dysregulation of chromobox proteins contributes to the progression of human diseases. CBX1 has been implicated in epigenetic control of chromatin structure and gene expression, but its role in human cancers remains largely unknown. Here we show that CBX1 exhibits oncogenic activities in hepatocellular carcinoma (HCC) and indicates poor outcomes. The expression of CBX1 was noticeably increased, at both mRNA and protein levels, in HCC tissues and cell lines, compared with the nontumorous ones. High CBX1 expression was significantly associated with larger tumor size, poor tumor differentiation and tumor vascular invasion. Patients with elevated expression of CBX1 were frequently accompanied with unfavorable overall and disease-free survivals in two independent cohorts consisting of 648 HCC cases. The prognostic value of CBX1 was further confirmed by stratified survival analyses. Multivariate cox regression model suggested CBX1 as an independent factor for overall survival (hazard ratio = 1.735, 95% confident interval: 1.342-2.244, P < .001). In vitro data demonstrated that CBX1 overexpression promoted cell proliferation and migration, whereas the knockdown of CBX1 resulted in the opposite phenotypes. Mechanistically, CBX1 interacted with transcription factor HMGA2 to activate the Wnt/β-Catenin signaling pathway. Suppression of β-Catenin by siRNA or specific inhibitor XAV-939 markedly attenuated CBX1-mediated cell growth. Collectively, our findings indicate that CBX1 functions as an oncogene and may serve as a potential prognostic biomarker in HCC.

journal_name

Transl Oncol

journal_title

Translational oncology

authors

Yang YF,Pan YH,Tian QH,Wu DC,Su SG

doi

10.1016/j.tranon.2018.07.002

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

1110-1118

issue

5

issn

1936-5233

pii

S1936-5233(18)30123-2

journal_volume

11

pub_type

杂志文章

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