Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Han, Xiaoying, Yang, Jing, Li, Dong, Guo, Zewei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cognizant Communication Corporation 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848443/
https://www.ncbi.nlm.nih.gov/pubmed/29523220
http://dx.doi.org/10.3727/096504018X15199489058224
_version_ 1783645138037243904
author Han, Xiaoying
Yang, Jing
Li, Dong
Guo, Zewei
author_facet Han, Xiaoying
Yang, Jing
Li, Dong
Guo, Zewei
author_sort Han, Xiaoying
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7848443
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Cognizant Communication Corporation
record_format MEDLINE/PubMed
spelling pubmed-78484432021-02-16 Overexpression of Uric Acid Transporter SLC2A9 Inhibits Proliferation of Hepatocellular Carcinoma Cells Han, Xiaoying Yang, Jing Li, Dong Guo, Zewei Oncol Res Article 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. Cognizant Communication Corporation 2019-05-07 /pmc/articles/PMC7848443/ /pubmed/29523220 http://dx.doi.org/10.3727/096504018X15199489058224 Text en Copyright © 2019 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License.
spellingShingle Article
Han, Xiaoying
Yang, Jing
Li, Dong
Guo, Zewei
Overexpression of Uric Acid Transporter SLC2A9 Inhibits Proliferation of Hepatocellular Carcinoma Cells
title Overexpression of Uric Acid Transporter SLC2A9 Inhibits Proliferation of Hepatocellular Carcinoma Cells
title_full Overexpression of Uric Acid Transporter SLC2A9 Inhibits Proliferation of Hepatocellular Carcinoma Cells
title_fullStr Overexpression of Uric Acid Transporter SLC2A9 Inhibits Proliferation of Hepatocellular Carcinoma Cells
title_full_unstemmed Overexpression of Uric Acid Transporter SLC2A9 Inhibits Proliferation of Hepatocellular Carcinoma Cells
title_short Overexpression of Uric Acid Transporter SLC2A9 Inhibits Proliferation of Hepatocellular Carcinoma Cells
title_sort overexpression of uric acid transporter slc2a9 inhibits proliferation of hepatocellular carcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848443/
https://www.ncbi.nlm.nih.gov/pubmed/29523220
http://dx.doi.org/10.3727/096504018X15199489058224
work_keys_str_mv AT hanxiaoying overexpressionofuricacidtransporterslc2a9inhibitsproliferationofhepatocellularcarcinomacells
AT yangjing overexpressionofuricacidtransporterslc2a9inhibitsproliferationofhepatocellularcarcinomacells
AT lidong overexpressionofuricacidtransporterslc2a9inhibitsproliferationofhepatocellularcarcinomacells
AT guozewei overexpressionofuricacidtransporterslc2a9inhibitsproliferationofhepatocellularcarcinomacells