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Open Access Overexpression of Uric Acid Transporter SLC2A9 Inhibits Proliferation of Hepatocellular Carcinoma Cells

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Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide. Although the mechanisms of HCC progression are not well understood, recent studies demonstrated the potential contribution of uric acid transporter SLC2A9 to tumor suppression. However, the roles and underlying mechanisms are still unknown. We aimed to study the roles and mechanisms of SLC2A9 in HCC. The present study showed that SLC2A9 expression was decreased in human HCC tissues and cell lines. In addition, overexpression of SLC2A9 inhibited HCC cell proliferation. SCL2A9 induced HCC cell apoptosis by inhibiting the expression of caspase 3. Our study also revealed that upregulation of SLC2A9 reduced intracellular reactive oxygen species (ROS) accumulation. Furthermore, SLC2A9 increased the mRNA and protein expression of tumor suppressor p53 in HCC cells. Probenecid inhibits SLC2A9-mediated uric acid transport, which promotes cell proliferation, inhibits cell apoptosis, induces intracellular ROS, and decreases the expression of p53 in HCC cells. Therefore, the present study demonstrated that SLC2A9 may be a novel tumor suppressor gene and a potential therapeutic target in HCC.
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Keywords: Apoptosis; Cell proliferation; HCC; P53; ROS; SLC2A9

Document Type: Research Article

Affiliations: 1: Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, P.R. China 2: Department of Oncology, Xuzhou City Hospital of Traditional Chinese Medicine, Xuzhou, P.R. China 3: Department of Oncology, Xuzhou Central Hospital, Xuzhou, Jiangsu, P.R. China 4: Department of Internal Medicine, Huangshan Traditional Chinese Medicine, Huangshan, Anhui, P.R. China

Publication date: May 7, 2019

This article was made available online on March 9, 2018 as a Fast Track article with title: "Overexpression of uric acid transporter SLC2A9 inhibits proliferation of hepatocellular carcinoma cells".

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