Oncotarget

Research Papers:

Nuclear receptor retinoid-related orphan receptor alpha promotes apoptosis but is reduced in human gastric cancer

Zhengguang Wang _, Fangyuan Xiong, Xiaoshan Wang, Yijun Qi, Haoyuan Yu, Yong Zhu and Huaqing Zhu

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Oncotarget. 2017; 8:11105-11113. https://doi.org/10.18632/oncotarget.14364

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Abstract

Zhengguang Wang1, Fangyuan Xiong2, Xiaoshan Wang1, Yijun Qi1, Haoyuan Yu1, Yong Zhu1, Huaqing Zhu2

1Department of Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China

2Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, Anhui, P.R. China

Correspondence to:

Zhengguang Wang, email: [email protected]

Keywords: gastric carcinoma, RORα, AMPK, apoptosis, chemotherapy resistance

Received: November 02, 2016     Accepted: December 23, 2016     Published: December 29, 2016

ABSTRACT

Retinoid-related orphan receptor α (RORα) is a nuclear receptor, which regulates inflammation and immune responses, lipid metabolism and circadian rhythm. Although RORα suppresses breast tumor invasion, it is unknown whether RORα is dysregulated in gastric cancer leading to cellular survival. Therefore, we hypothesize that RORα is dysfunctional in gastric carcinoma and this causes decreased apoptosis in gastric cancer cells. To test this hypothesis, we employed human gastric cancer tissues with different stages to determine RORα expression, as well as in vitro human gastric cancer cells to determine how RORα is reduced during apoptosis. We found that the expression of RORα was reduced in gastric tissues with cancer, and this correlated with increased TNM stages. The mechanisms underlying RORα reduction is due to the reduced activation of AMP-activated protein kinase (AMPK), as a selective AMPK activator AICAR increased RORα activation and level in human gastric cancer cells. Furthermore, AICAR treatment increased RORα recruitment on the promoters of tumor suppressor genes (i.e., FBXM7, SEMA3F and p21) leading to apoptosis in human gastric cancer cells. Taken together, RORα reduction occurs in gastric cancer leading to the survival of tumor cells, which is attenuated by AMPK. Therefore, both RORα and AMPK are potential targets for the intervention and therapy in gastric carcinoma.


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