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miR-520a-3p 通过靶向 SUV39H1 表达抑制上皮性卵巢癌的恶性进展。

MiR-520a-3p inhibits malignant progression of epithelial ovarian cancer by targeting SUV39H1 expression.

机构信息

Department of Gynaecology and Obstetrics, Jinshan Hospital affiliated to Fudan University, No.1508 Longhang Road, Shanghai, 201508, China.

出版信息

Hum Cell. 2021 Mar;34(2):570-578. doi: 10.1007/s13577-020-00455-2. Epub 2020 Nov 16.

Abstract

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.

摘要

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。

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