Research Papers:
MicroRNA-222-3p/GNAI2/AKT axis inhibits epithelial ovarian cancer cell growth and associates with good overall survival
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Abstract
Xiaodan Fu1,2, Yimin Li1,2, Ayesha Alvero3, Juanni Li1,2, Qihui Wu1,2, Qing Xiao1,2, Yulong Peng1,2, Yongbin Hu1,2, Xiang Li1,2, Wenguang Yan5, Ke Guo6, Wenjuan Zhou7, Yong Wang8, Junwen Liu9, Yu Zhang4, Gil Mor3, Jifang Wen1,2, Gang Yin1,2
1Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
2Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China
3Department of Obstetrics, Gynecology and Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, New Haven, CT, USA
4Department of Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
5Department of Rehabilitation, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China
6Department of Internal Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China
7School of Nursing, Central South University, Changsha, Hunan Province, China
8Department of Immunology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China
9Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China
Correspondence to:
Gang Yin, email: [email protected]
Jifang Wen, email: [email protected]
Keywords: ovarian cancer, miR-222-3p, GNAI2, pAKT, cell growth
Received: June 19, 2016 Accepted: October 22, 2016 Published: November 02, 2016
ABSTRACT
Ovarian carcinoma is the most lethal gynecologic tumor worldwide. Despite having developed molecular diagnostic tools and targeted therapies over the past few decades, patient survival is still quite poor. Numerous studies suggest that microRNAs are key regulators of many fundamental biological processes, including neoplasia and tumor progression. miR-222 is one of those miRNAs that has attracted much attention for its multiple roles in human diseases, especially cancer. The potential role of microRNAs in ovarian cancer has attracted much attention in recent years. Some of these microRNAs have been suggested as potential therapeutic targets for EOC patients. In this study, we sought to investigate the biologic functions of miR-222-3p in EOC carcinogenesis. Herein, we examined the expression of miR-222-3p in EOC patients, mouse models and cell lines, and found that higher expression of miR-222-3p was associated with better overall survival in EOC patients, and its level was negatively correlated with tumor growth in vivo. Furthermore, in-vitro experiments indicated that miR-222-3p inhibited EOC cell proliferation and migration, and decreased the phosphorylation of AKT. We identified GNAI2 as a target of miR-222-3p. We also found that GNAI2 promoted EOC cell proliferation, and is an activator of the PI3K/AKT pathway. We describe the characterization of a novel regulatory axis in ovarian cancer cells, miR-222-3p/GNAI2/AKT and its potential application as a therapeutic target for EOC patients.
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