Department of Immunology, Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China.
Cell Death Dis. 2018 Nov 8;9(11):1123. doi: 10.1038/s41419-018-1093-9.
Epithelial ovarian carcinoma (EOC) is the most lethal gynecologic malignancy. However, the molecular mechanisms remain unclear. In this study, we found that miR-146b was downregulated in EOC and its expression level was negatively correlated with the pathological staging. Follow-up functional experiments illustrated that overexpression of miR-146b significantly inhibited cell migration and invasion, and increased cell proliferation, but it also improved the response to chemotherapeutic agents. Mechanistically, we demonstrated that miR-146b exerted its function mainly through inhibiting F-box and leucine-rich repeat protein 10 (FBXL10), and upregulated the Cyclin D1, vimentin (VIM), and zona-occludens-1 (ZO-1) expression in EOC. These findings indicate that miR-146b-FBXL10 axis is an important epigenetic regulation pathway in EOC. Low miR-146b may contribute to cancer progression from primary stage to advanced stage, and may be the promising therapeutic target of EOC.
上皮性卵巢癌 (EOC) 是最致命的妇科恶性肿瘤。然而，其分子机制尚不清楚。在本研究中，我们发现 miR-146b 在 EOC 中表达下调，其表达水平与病理分期呈负相关。后续的功能实验表明，miR-146b 的过表达显著抑制了细胞迁移和侵袭，同时增加了细胞增殖，但也提高了对化疗药物的反应。从机制上讲，我们证明 miR-146b 主要通过抑制 F-box 和富含亮氨酸重复蛋白 10 (FBXL10) 发挥其功能，并在上皮性卵巢癌中上调细胞周期蛋白 D1、波形蛋白 (VIM) 和紧密连接蛋白-1 (ZO-1) 的表达。这些发现表明 miR-146b-FBXL10 轴是 EOC 中重要的表观遗传调控途径。低水平的 miR-146b 可能导致癌症从早期阶段进展到晚期阶段，并且可能是 EOC 有前途的治疗靶点。
