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Hepatitis B virus X protein-induced SH2 domain-containing 5 (SH2D5) expression promotes hepatoma cell growth via an SH2D5-transketolase interaction.

ABSTRACT: Hepatitis B virus X protein (HBx) critically contributes to the development of hepatocellular carcinoma (HCC). However, the mechanisms by which HBx promotes HCC remain unclear. In the present study, using a combination of gene expression profiling and immunohistochemistry, we found higher levels of SH2 domain-containing 5 (SH2D5) in liver tissue from HBV-associated HCC (HBV-HCC) patients than in adjacent nontumor tissues. Moreover, HBV infection elevated SH2D5 levels, and we observed that HBx plays an important role in SH2D5 induction. We also found that HBx triggers SH2D5 expression through the NF-?B and c-Jun kinase pathways. Employing SH2D5 overexpression or knockdown, we further demonstrate that SH2D5 promotes HCC cell proliferation both in vitro and in vivo While investigating the mechanism of SH2D5-mediated stimulation of HCC cell proliferation, we noted that HBV induces SH2D5 binding to transketolase (TKT), a pentose phosphate pathway enzyme, thereby promoting an interaction between and signal transducer and activator of transcription 3 (STAT3). Furthermore, HBx stimulated STAT3 phosphorylation at Tyr-705 and promoted the activity and downstream signaling pathway of STAT3 via the SH2D5-TKT interaction. Taken together, our results suggest that SH2D5 is an HBV-induced protein capable of binding to TKT, leading to induction of HCC cell proliferation.

SUBMITTER: Zheng Y

PROVIDER: S-EPMC6442033 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Hepatitis B virus X protein-induced SH2 domain-containing 5 (SH2D5) expression promotes hepatoma cell growth via an SH2D5-transketolase interaction.

Zheng Yongfa Y Ming Pingpo P Zhu Chengliang C Si Yu Y Xu Shilei S Chen Aidong A Wang Jun J Zhang Binghong B

The Journal of biological chemistry 20190118 13

Hepatitis B virus X protein (HBx) critically contributes to the development of hepatocellular carcinoma (HCC). However, the mechanisms by which HBx promotes HCC remain unclear. In the present study, using a combination of gene expression profiling and immunohistochemistry, we found higher levels of SH2 domain-containing 5 (SH2D5) in liver tissue from HBV-associated HCC (HBV-HCC) patients than in adjacent nontumor tissues. Moreover, HBV infection elevated SH2D5 levels, and we observed that HBx pl ...[more]

PMID: 30659097

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Dataset Information

Hepatitis B virus X protein-induced SH2 domain-containing 5 (SH2D5) expression promotes hepatoma cell growth via an SH2D5-transketolase interaction.

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Hepatitis B virus X protein-induced SH2 domain-containing 5 (SH2D5) expression promotes hepatoma cell growth via an SH2D5-transketolase interaction.

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