CENP-H regulates the cell growth of human hepatocellular carcinoma cells through the mitochondrial apoptotic pathway

Lu,Guifang; Hou,Helei; Lu,Xinlan; Ke,Xiquan; Wang,Xin; Zhang,Dan; Zhao,Yan; Zhang,Jun; Ren,Mudan; He,Shuixiang

doi:10.3892/or.2017.5602

CENP-H regulates the cell growth of human hepatocellular carcinoma cells through the mitochondrial apoptotic pathway

Authors:
- Guifang Lu
- Helei Hou
- Xinlan Lu
- Xiquan Ke
- Xin Wang
- Dan Zhang
- Yan Zhao
- Jun Zhang
- Mudan Ren
- Shuixiang He
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Affiliations: Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Medical Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
Published online on: April 26, 2017 https://doi.org/10.3892/or.2017.5602
Pages: 3484-3492

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Abstract

The genomic alterations of hepatocellular carcinoma (HCC) are still unclear. Centromere protein-H (CENP-H) has been shown to be associated with many solid tumors. Our previous study found that CENP-H was upregulated in HCC and was related to patient prognosis. However, the biological functions of CENP-H in HCC and the possible underlying mechanisms have not been well elucidated. In the present study, we demonstrated that CENP-H knockdown inhibited the proliferation of Hep3B cells and decreased colony formation ability of single cells in vitro. Furthermore, CENP-H knockdown induced Hep3B cell apoptosis, and apoptotic bodies were observed using transmission electron microscopy. The protein expression of cleaved caspase-3 was upregulated in Hep3B cells after CENP-H knockdown. Additionally, a Bax/Bcl-2 ratio imbalance with a significant increase of Bax and a substantial decrease of Bcl-2 at both the mRNA and protein levels were determined in this study. In an animal experiment, CENP-H knockdown blocked the growth of Hep3B subcutaneous xenografts. Immunohistochemistry revealed that the protein expression of cleaved caspase-3 and Bax was increased, whereas the protein expression of Bcl-2 and Ki-67 was decreased in subcutaneous xenografts of the CENP-H-knockdown group. In summary, CENP-H may be involved in cell proliferation and apoptosis of HCC cells through the mitochondrial apoptotic pathway. Combined with previous studies, the data provide a new perspective on HCC development and progression.

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