Zhang Yiting, Zhu Xinyue, Zhu Xiaomin, Wu Yan, Liu Yajun, Yao Borui, Huang Zhenping
1 Department of Ophthalmology, Medical School of Nanjing University, Jinling Hospital, Nanjing, China.
2 Department of Ophthalmology, Jinling Hospital, Nanjing, China.
Tumour Biol. 2017 Mar;39(3):1010428317691674. doi: 10.1177/1010428317691674.
Retinoblastoma is a common intraocular malignancy that occurs during childhood. MicroRNAs play critical roles in the regulation of retinoblastoma initiation and progression, and aberrant expression of miR-613 had been reported in various types of cancer. However, the role and mechanism of its function in retinoblastoma are still unclear. In this study, we found that miR-613 was downregulated in retinoblastoma tissues and cell lines. Overexpression of miR-613 suppressed retinoblastoma cell proliferation, migration, and invasion and induced cell cycle arrest in vitro. Additionally, overexpressed miR-613 also inhibited tumor formation of retinoblastoma cells in vivo. We further identified E2F5 as a direct target of miR-613. Reintroduction of E2F5 without 3'-untranslated region reversed the inhibitory effects of miR-613 on cell proliferation and invasion. Our data collectively indicate that miR-613 functions as a tumor suppressor in retinoblastoma through downregulating E2F5, supporting the targeting of the novel miR-613/E2F5 axis as a potentially effective therapeutic approach for retinoblastoma.
视网膜母细胞瘤是一种常见于儿童期的眼内恶性肿瘤。微小RNA在视网膜母细胞瘤的发生和发展调控中发挥关键作用,并且已有报道称miR - 613在多种类型的癌症中存在异常表达。然而,其在视网膜母细胞瘤中的作用及功能机制仍不清楚。在本研究中,我们发现miR - 613在视网膜母细胞瘤组织和细胞系中表达下调。miR - 613的过表达在体外抑制了视网膜母细胞瘤细胞的增殖、迁移和侵袭,并诱导细胞周期停滞。此外,过表达的miR - 613在体内也抑制了视网膜母细胞瘤细胞的肿瘤形成。我们进一步确定E2F5是miR - 613的直接靶点。重新导入没有3' - 非翻译区的E2F5可逆转miR - 613对细胞增殖和侵袭的抑制作用。我们的数据共同表明,miR - 613通过下调E2F5在视网膜母细胞瘤中发挥肿瘤抑制作用,支持将新型miR - 613 / E2F5轴作为视网膜母细胞瘤潜在有效的治疗靶点。