Downregulated ADARB1 Facilitates Cell Proliferation, Invasion and has Effect on the Immune Regulation in Ovarian Cancer

Wei Zhu; Zhijie Xu; Meiyuan Huang; Xiang Wang; Xinxin Ren; Yuan Cai; Bi Peng; Qiuju Liang; Xi Chen; Yuanliang Yan

doi:10.3389/fbioe.2021.792911

Downregulated ADARB1 Facilitates Cell Proliferation, Invasion and has Effect on the Immune Regulation in Ovarian Cancer

Front Bioeng Biotechnol. 2021 Dec 23:9:792911. doi: 10.3389/fbioe.2021.792911. eCollection 2021.

Authors

Wei Zhu¹, Zhijie Xu^{1

2}, Meiyuan Huang³, Xiang Wang⁴, Xinxin Ren⁵, Yuan Cai¹, Bi Peng¹, Qiuju Liang⁴, Xi Chen⁴, Yuanliang Yan⁴

Affiliations

¹ Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
³ Department of Pathology, The Affiliated Zhuzhou Hospital Xiangya Medical College, Central South University, Zhuzhou, China.
⁴ Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
⁵ Key Laboratory of Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China.

Abstract

Ovarian cancer (OC) is typically diagnosed at an advanced stage and poses a significant challenge to treatment and recovery. Rencently, Adenosine deaminase RNA-specific B1 (ADARB1), an adenosine-to-inosine (A-to-I) RNA-editing enzyme, has been found to play an essential role in the development of cancer. However, the specific function of ADARB1 in ovarian cancer is still not fully understood. Here, we investigated the effects of ADARB1 on OC biology. By conducting bioinformatics analyses of several public databases, we found significantly decreased ADARB1 expression in OC cells and tissues. Moreover, RT-PCR and western blot showed lower ADARB1 expression in OVCAR3, HO8910pm and A2780 OC cells compared to human normal ovarian epithelial cell IOSE. Cell proliferation assay and clone formation assay showed that overexpression of ADARB1 (ADARB1-OE) inhibited the proliferation of tumor cells. Wound healing and transwell assay indicated that ADARB1-OE could suppress OC cell invasion and metastasis. Kaplan-Meier methods revealed that the patients with low level of ADARB1 displayed poor prognosis. TISIDB databases were further used to analyze the roles of ADARB1 in tumor-immune system interactions in OC patients. Furthermore, ADARB1-OE down-regulated the expression of phosphorylated AKT. Combination of ADARB1-OE and AKT inhibitor MK2206 exerted stronger cell growth inhibition. Thus, our investigation demonstrated that low levels of ADARB1 might be a potential target in the tumorigenesis and prognostic evaluation of OC patients.

Keywords: ADARB1; Akt; cell growth; immune regulation; ovarian cancer.