Oncotarget

Research Papers:

IL-23 enhances the malignant properties of hepatoma cells by attenuation of HNF4α

Qing Jiang, Yuanli Sun, Zilong Guo, Ru Chen, Simin Ma, Mingpeng Fu, Huifen Zhu, Qin Ning, Ping Lei _ and Guanxin Shen

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Oncotarget. 2018; 9:28309-28321. https://doi.org/10.18632/oncotarget.24875

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Abstract

Qing Jiang1,2,*, Yuanli Sun1,*, Zilong Guo1, Ru Chen1, Simin Ma1, Mingpeng Fu1, Huifen Zhu1, Qin Ning3, Ping Lei1 and Guanxin Shen1

1Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

2Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

3Department of Infectious Disease, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

*Authors contributed equally to this work

Correspondence to:

Ping Lei, email: adaleip@hust.edu.cn

Guanxin Shen, email: myjsz@tjmu.edu.cn

Keywords: IL-23; hepatocyte nuclear factor 4α; HBV; tumor progression

Received: April 03, 2017     Accepted: March 06, 2018     Published: June 19, 2018

ABSTRACT

Chronic infection with hepatitis B virus (HBV) is one of the major risk factors for hepatocellular carcinoma. HBV infection can induce the expression of IL-23. However, the effects of IL-23 on carcinogenesis are rare and contradictory. To investigate the potential role of IL-23 on malignant properties of hepatoma cells, in the present study, first, we confirmed that HBV drove infected hepatoma cells to produce more IL-23. And then we found that at low concentration, human recombinant IL-23 (hrIL-23) enhanced malignant properties of hepatoma cells through increasing the proportion of stem/progenitor cells, promoting proliferation and colony formation, reducing apoptosis and inducing motility and invasivity of them. Hepatocyte nuclear factor 4 alpha (HNF4α), which is essential for liver development and hepatocyte function, was found to be downregulated in HBV integrated or transiently transfected hepatoma cells. Its expression was also decreased in cells treated by hrIL-23 or by HepG2.215 culture supernatant and this decrease could be abolished by supplementation of anti-IL-23p19 antibody. Hence, it is speculated that HBV related IL-23 can enhance malignant properties of hepatoma cells through attenuation of HNF4α. The findings identified a potential target of interventional strategies for treating hepatitis B patients through manipulation of the IL-23.


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