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      CBX2 Regulates Proliferation and Apoptosis via the Phosphorylation of YAP in Hepatocellular Carcinoma

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          Abstract

          Chromobox 2 (CBX2), a chromobox family protein, is a crucial component of the polycomb group complex: polycomb repressive complex 1 (PRC1). Research on CBX2 as an oncogene has been published in recent years. However, the connection between CBX2 and hepatocellular carcinoma (HCC) has not been studied. In this article, based on the results of immunohistochemical (IHC) staining of HCC and adjacent liver tissue microarrays, we found that high CBX2 expression is associated with poor prognosis in HCC patients. The results of a CCK8 assay, a clonogenic survival assay and a nude mouse tumorigenicity assay showed that knockdown of CBX2 inhibited the proliferation of HCC cells. According to the results of Annexin V-FITC/propidium iodide (PI) staining-based fluorescence activated cell sorting (FACS) analysis, knockdown of CBX2 increased HCC cell apoptosis. Furthermore, the RNA-seq results revealed that knockdown of CBX2 inhibited the expression of WTIP, which is an inhibitor of the Hippo pathway. We used western blotting to validate the mechanism and discovered that knockdown of CBX2 increased the phosphorylation of YAP, which explains why knockdown of CBX2 inhibits proliferation and increases apoptosis in HCC cells. In conclusion, CBX2 could be a potential target for HCC anticancer treatment.

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          Most cited references23

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          Polycomb silencers control cell fate, development and cancer.

          Polycomb group (PcG) proteins are epigenetic gene silencers that are implicated in neoplastic development. Their oncogenic function might be associated with their well-established role in the maintenance of embryonic and adult stem cells. In this review, we discuss new insights into the possible mechanisms by which PcGs regulate cellular identity, and speculate how these functions might be relevant during tumorigenesis.
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            The cancer epigenome: Concepts, challenges, and therapeutic opportunities

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              YAP activation is an early event and a potential therapeutic target in liver cancer development.

              Although the growth suppressing Hippo pathway has been implicated in hepatocellular carcinoma (HCC) pathogenesis, it is unknown at which stage of hepatocarcinogenesis its dysregulation occurs. We investigated in rat and human preneoplastic lesions whether overexpression of the transcriptional co-activator Yes-associated protein (YAP) is an early event.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2019
                2 June 2019
                : 10
                : 12
                : 2706-2719
                Affiliations
                [1 ]Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
                [2 ]Department of Vascular Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
                [3 ]Department of Pulmonary Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
                Author notes
                ✉ Corresponding authors: Liming Wang, e-mail: wangbcc259@ 123456163.com ; Qi Wang, e-mail: wqdlmu@ 123456163.com

                *These authors have contributed equally to this work

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav10p2706
                10.7150/jca.31845
                6584921
                31258779
                e624cc43-252a-4c66-8eae-c6f4ac46acfc
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 28 November 2018
                : 9 May 2019
                Categories
                Research Paper

                Oncology & Radiotherapy
                chromobox 2 (cbx2),hepatocellular carcinoma (hcc),hippo pathway,yes-associated protein (yap)

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