Department of Gynaecology and Obstetrics, Jinshan Hospital affiliated to Fudan University, No.1508 Longhang Road, Shanghai, 201508, China.
Hum Cell. 2021 Mar;34(2):570-578. doi: 10.1007/s13577-020-00455-2. Epub 2020 Nov 16.
Downregulation of microRNA-520a-3p (miR-520a-3p) has been demonstrated in several cancers, and miR-520a-3p has been shown to inhibit tumor progression, indicating its potential role as a tumor suppressor. In this study, we found that miR-520a-3p was also downregulated in epithelial ovarian cancer (EOC) tissues and cell lines. Functional assays showed that ectopic expression of miR-520a-3p suppressed EOC cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) and induced cell cycle arrest in vitro. Similarly, overexpression of miR-520a-3p inhibited tumor growth and metastasis in vivo. Mechanistically, suppressor of variegation 39H1 (SUV39H1) was identified as a novel target of miR-520a-3p through biomedical databases and dual-luciferase reporter assay. Subsequently, SUV39H1 was observed to be negatively regulated by miR-520a-3p at the mRNA and protein levels, and inversely correlated with miR-520a-3p expression in EOC tissues. Furthermore, overexpression of SUV39H1 reversed the suppressive effects of miR-520a-3p in EOC cells. Collectively, these results suggest that the miR-520a-3p/SUV39H1 axis may contribute to EOC cell proliferation and metastasis, revealing miR-520a-3p as a potential therapeutic target for the treatment of EOC.
miR-520a-3p(微小 RNA-520a-3p)在几种癌症中下调,miR-520a-3p 被证明可以抑制肿瘤进展,表明其作为肿瘤抑制因子的潜在作用。在这项研究中,我们发现 miR-520a-3p 在卵巢上皮癌(EOC)组织和细胞系中也下调。功能测定表明,miR-520a-3p 的异位表达抑制 EOC 细胞增殖、侵袭和上皮间质转化(EMT),并在体外诱导细胞周期停滞。同样,miR-520a-3p 的过表达抑制体内肿瘤生长和转移。机制上,通过生物医学数据库和双荧光素酶报告基因测定,鉴定出 SUV39H1(杂合性缺失 39H1)为 miR-520a-3p 的一个新的靶基因。随后观察到 SUV39H1 在 mRNA 和蛋白水平上受 miR-520a-3p 的负调控,与 EOC 组织中 miR-520a-3p 的表达呈负相关。此外,SUV39H1 的过表达逆转了 miR-520a-3p 对 EOC 细胞的抑制作用。总之,这些结果表明,miR-520a-3p/SUV39H1 轴可能参与 EOC 细胞增殖和转移,揭示 miR-520a-3p 可能成为治疗 EOC 的潜在治疗靶点。