miR-219-5p 通过靶向 HMGA2 抑制卵巢癌细胞的生长和转移。
MiR-219-5p inhibits growth and metastasis of ovarian cancer cells by targeting HMGA2.
机构信息
Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital of Tongji University, Tongji University School of Medicine, No 301 Middle Yan Chang Road, Shanghai, 200072, China.
出版信息
Biol Res. 2018 Nov 24;51(1):50. doi: 10.1186/s40659-018-0199-y.
BACKGROUND
Accumulating studies have demonstrated that high-mobility group A2 (HMGA2), an oncofetal protein, plays a role in tumor development and progression. However, the molecular role of HMGA2 in ovarian carcinoma is yet to be established. MicroRNAs (miRNAs), a group of small noncoding RNAs, negatively regulate gene expression and their dysregulation has been implicated in tumorigenesis. The aim of this study was to investigate the potential involvement of a specific miRNA, miR-219-5p, in HMGA2-induced ovarian cancer.
METHODS
The ovarian cancer cell line, SKOV3, was employed, and miR-219-5p and HMGA2 overexpression vectors constructed. The CCK-8 kit was used to determine cell proliferation and the Transwell assay used to measure cell invasion and migration. RT-PCR and western blot analyses were applied to analyze the expression of miR-219-5p and HMGA2, and the luciferase reporter assay used to examine the interactions between miR-219-5p and HMGA2. Nude mice were employed to characterize in vivo tumor growth regulation.
RESULTS
Expression of miR-219-5p led to suppression of proliferation, invasion and migration of the ovarian cancer cell line, SKOV3, by targeting HMGA2. The inhibitory effects of miR-219-5p were reversed upon overexpression of HMGA2. Data from the luciferase reporter assay showed that miR-219-5p downregulates HMGA2 via direct integration with its 3'-UTR. Consistent with in vitro findings, expression of miR-219-5p led to significant inhibition of tumor growth in vivo.
CONCLUSION
Our results collectively suggest that miR-219-5p inhibits tumor growth and metastasis by targeting HMGA2.
背景
越来越多的研究表明，高迁移率族蛋白 A2（HMGA2）是一种癌胚蛋白，在肿瘤的发生和发展中起作用。然而，HMGA2 在卵巢癌中的分子作用尚未确定。microRNAs（miRNAs）是一组小的非编码 RNA，负调控基因表达，其失调与肿瘤发生有关。本研究旨在探讨特定 miRNA，miR-219-5p 在 HMGA2 诱导的卵巢癌中的潜在作用。
方法
使用卵巢癌细胞系 SKOV3，构建 miR-219-5p 和 HMGA2 过表达载体。CCK-8 试剂盒用于测定细胞增殖，Transwell 测定法用于测定细胞侵袭和迁移。应用 RT-PCR 和 Western blot 分析来分析 miR-219-5p 和 HMGA2 的表达，应用荧光素酶报告基因测定来检测 miR-219-5p 和 HMGA2 之间的相互作用。使用裸鼠来研究体内肿瘤生长的调控。
结果
miR-219-5p 的表达通过靶向 HMGA2 抑制卵巢癌细胞系 SKOV3 的增殖、侵袭和迁移。过表达 HMGA2 逆转了 miR-219-5p 的抑制作用。荧光素酶报告基因测定显示，miR-219-5p 通过与 HMGA2 的 3'-UTR 直接整合来下调 HMGA2。与体外研究结果一致，miR-219-5p 的表达导致体内肿瘤生长的显著抑制。
结论
我们的研究结果表明，miR-219-5p 通过靶向 HMGA2 抑制肿瘤生长和转移。
Zotero 插件