HIF‑1α regulates A2B adenosine receptor expression in liver cancer cells

Kwon,Jae Hyun; Lee,Jooyoung; Kim,Jiye; Jo,Yong Hwa; Kirchner,Varvara A.; Kim,Nayoung; Kwak,Bong Jun; Hwang,Shin; Song,Gi‑Won; Lee,Sung‑Gyu; Yoon,Young‑In; Park,Gil‑Chun; Tak,Eunyoung

doi:10.3892/etm.2019.8081

HIF‑1α regulates A2B adenosine receptor expression in liver cancer cells

Authors:
- Jae Hyun Kwon
- Jooyoung Lee
- Jiye Kim
- Yong Hwa Jo
- Varvara A. Kirchner
- Nayoung Kim
- Bong Jun Kwak
- Shin Hwang
- Gi‑Won Song
- Sung‑Gyu Lee
- Young‑In Yoon
- Gil‑Chun Park
- Eunyoung Tak
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Affiliations: Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea, Asan‑Minnesota Institute for Innovating Transplantation, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea, Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea, Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea, Division of Hepatobiliary‑Pancreas Surgery and Liver Transplantation, Department of Surgery, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
Published online on: October 7, 2019 https://doi.org/10.3892/etm.2019.8081
Pages: 4231-4240
Copyright: © Kwon et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver cancer exhibits the fourth most common cause of cancer‑associated mortality worldwide. Due to the rapid growth, solid tumors undergo severe hypoxia and produce high levels of extracellular adenosine to maintain homeostasis. A previous study indicated that the hypoxic condition in liver cancer increased hepatic adenosine, which is known to facilitate cancer survival and proliferation. Extracellular adenosine has been revealed to regulate pathological and physiological processes in cells and tissues. However, its pathophysiological role in liver cancer remains undetermined. Emerging evidence has indicated that the adenosine A2B receptor promotes the progression of liver cancer. Therefore, it was hypothesized that HIF‑1α is a transcriptional regulator of A2B in human liver cancer. The current study determined A2B expression of a number of liver cancer cell lines and performed functional studies of HIF‑1α as a master transcriptional regulator of hepatic A2B signaling during hypoxic conditions. The current study aimed to identify the promoter region of A2B, which has a hypoxia response element, by performing luciferase assays. The present study demonstrated that reduced HIF‑1α expression is associated with low expression of A2B, and HIF‑1α overexpression is associated with A2B induction. Furthermore, the siRNA‑mediated downregulation of A2B inhibited the growth and proliferation of HepG2, which is a liver cancer cell line. The relationship between HIF‑1α and A2B expression was also identified in human liver cancer specimens. In conclusion, the current study indicated that A2B is induced by the HIF‑1α transcriptional regulator during hypoxia, and it may be a potential pharmacologic and therapeutic target for the treatment of patients with liver cancer.

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