MicroRNA-222-3p/GNAI2/AKT axis inhibits epithelial ovarian cancer cell growth and associates with good overall survival.
MicroRNA-222-3p/GNAI2/AKT axis inhibits epithelial ovarian cancer cell growth and associates with good overall survival.
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DOI：
10.18632/oncotarget.13017
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发表时间：
2016-12-06
期刊：
影响因子：
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通讯作者：
Yin G
中科院分区：
文献类型：
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作者：
Fu X;Li Y;Alvero A;Li J;Wu Q;Xiao Q;Peng Y;Hu Y;Li X;Yan W;Guo K;Zhou W;Wang Y;Liu J;Zhang Y;Mor G;Wen J;Yin G
卵巢癌是世界上最致命的妇科肿瘤。尽管在过去的几十年里已经开发了分子诊断工具和靶向治疗，但患者的存活率仍然相当低。大量研究表明，microRNAs是许多基本生物学过程的关键调节因子，包括肿瘤形成和肿瘤进展。MiR-222是其中一种在人类疾病，特别是癌症中发挥多种作用的miRNAs。近年来，microRNAs在卵巢癌中的潜在作用引起了人们的极大关注。其中一些微小RNA已被认为是卵巢癌患者的潜在治疗靶点。本研究旨在探讨miR-222-3p在卵巢癌发生中的生物学作用。在此，我们检测了miR-222-3p在卵巢癌患者、小鼠模型和细胞系中的表达，发现miR-222-3p的高表达与卵巢癌患者的总体生存有关，其水平与体内肿瘤的生长呈负相关。此外，体外实验表明miR-222-3p抑制EoC细胞的增殖和迁移，并降低AKT的磷酸化。我们将GNAI2确定为miR-222-3p的靶标。我们还发现GNAI2促进了EoC细胞的增殖，并且是PI3K/AKT通路的激活剂。我们描述了卵巢癌细胞中一个新的调节轴miR-222-3p/GNAI2/AKT的特征及其作为卵巢癌患者治疗靶点的潜在应用。
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.