MicroRNA-222-3p/GNAI2/AKT axis inhibits epithelial ovarian cancer cell growth and associates with good overall survival.
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.
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.|Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
Xiaodan
X
Fu
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.|Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
Yimin
Y
Li
Department of Obstetrics, Gynecology and Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, New Haven, CT, USA.
Ayesha
A
Alvero
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.|Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
Juanni
J
Li
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.|Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
Qihui
Q
Wu
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.|Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
Qing
Q
Xiao
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.|Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
Yulong
Y
Peng
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.|Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
Yongbin
Y
Hu
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.|Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
Xiang
X
Li
Department of Rehabilitation, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Wenguang
W
Yan
Department of Internal Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Ke
K
Guo
School of Nursing, Central South University, Changsha, Hunan Province, China.
Wenjuan
W
Zhou
Department of Immunology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
Yong
Y
Wang
Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
Junwen
J
Liu
Department of Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Yu
Y
Zhang
Department of Obstetrics, Gynecology and Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, New Haven, CT, USA.
Gil
G
Mor
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.|Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
Jifang
J
Wen
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.|Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.
Gang
G
Yin
D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000818:Animals; D001665:Binding Sites; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D010766:Phosphorylation; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D055815:Young Adult
D020413:3' Untranslated Regions; D051960:GTP-Binding Protein alpha Subunit, Gi2; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; C525710:MIR222, human; C498015:GNAI2 protein, human
GNAI2; cell growth; miR-222-3p; ovarian cancer; pAKT