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Oncotarget. 2016 Dec 6;7(49):80633-80654. doi: 10.18632/oncotarget.13017.

MicroRNA-222-3p/GNAI2/AKT axis inhibits epithelial ovarian cancer cell growth and associates with good overall survival.

Fu X1,2, Li Y1,2, Alvero A3, Li J1,2, Wu Q1,2, Xiao Q1,2, Peng Y1,2, Hu Y1,2, Li X1,2, Yan W4, Guo K5, Zhou W6, Wang Y7, Liu J8, Zhang Y9, Mor G3, Wen J1,2, Yin G1,2.

Author information

1
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
2
Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
3
Department of Obstetrics, Gynecology and Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, New Haven, CT, USA.
4
Department of Rehabilitation, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
5
Department of Internal Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
6
School of Nursing, Central South University, Changsha, Hunan Province, China.
7
Department of Immunology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
8
Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
9
Department of Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.

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.

KEYWORDS:

GNAI2; cell growth; miR-222-3p; ovarian cancer; pAKT

PMID:
27811362
PMCID:
PMC5348346
DOI:
10.18632/oncotarget.13017
[Indexed for MEDLINE]
Free PMC Article

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