Li Shaoru, Li Yan, Wen Zhengfang, Kong Fanjing, Guan Xinlei, Liu Wenhui
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
Department of Endocrinology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
Mol Med Rep. 2014 May;9(5):1703-8. doi: 10.3892/mmr.2014.2021. Epub 2014 Mar 6.
The expression levels of estrogen receptor (ER α) are closely associated with estrogen-dependent growth, invasion and response to endocrine therapy in ERα-positive ovarian cancer. However, the underlying regulatory mechanisms remain to be fully understood. Previous studies have demonstrated that ERα is a direct target of microRNA (miR)-206. miR-206 has been found to be an important tumor suppressor in several cancer types, including ovarian, gastric and laryngeal cancer. However, the specific role of miR-206 in ovarian cancer remains unclear. The aim of the present study was to investigate the role of miR-206 in ER-a positive ovarian cancer in vitro. The present study demonstrated that miR-206 is significantly downregulated in ERα-positive but not ERα‑negative ovarian cancer tissues, compared with normal ovarian epithelium tissue. It was also found that the expression of miR-206 was decreased in ERα-positive ovarian cancer cell lines, CAOV-3 and BG-1, compared with normal ovarian epithelium tissues. This suggests that miR-206 may play a role in ERα-positive ovarian cancer cells via an estrogen-dependent mechanism. Further analysis revealed that 17β-E2 treatment significantly promoted cellular proliferation and invasion of estrogen-dependent CAOV-3 and BG-1 cells, which could be reversed by the introduction of miR-206 mimics. In conclusion, the present study suggests that miR-206 has an inhibitory role in estrogen-dependent ovarian cancer cells. Thus, miR-206 may be a promising candidate for the endocrine therapy of ERα-positive ovarian cancer.
雌激素受体(ERα)的表达水平与ERα阳性卵巢癌中雌激素依赖的生长、侵袭及对内分泌治疗的反应密切相关。然而,其潜在的调控机制仍有待充分了解。既往研究表明,ERα是微小RNA(miR)-206的直接靶点。已发现miR-206在包括卵巢癌、胃癌和喉癌在内的多种癌症类型中是一种重要的肿瘤抑制因子。然而,miR-206在卵巢癌中的具体作用仍不清楚。本研究的目的是在体外研究miR-206在ERα阳性卵巢癌中的作用。本研究表明,与正常卵巢上皮组织相比,miR-206在ERα阳性而非ERα阴性的卵巢癌组织中显著下调。还发现,与正常卵巢上皮组织相比,ERα阳性卵巢癌细胞系CAOV-3和BG-1中miR-206的表达降低。这表明miR-206可能通过雌激素依赖机制在ERα阳性卵巢癌细胞中发挥作用。进一步分析显示,17β-E2处理显著促进了雌激素依赖的CAOV-3和BG-1细胞的增殖和侵袭,而引入miR-206模拟物可逆转这种作用。总之,本研究表明miR-206在雌激素依赖的卵巢癌细胞中具有抑制作用。因此,miR-206可能是ERα阳性卵巢癌内分泌治疗的一个有前景的候选者。