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miR-421靶向KDM5A在人卵巢癌中抑制卵巢癌细胞的进展。

Targeting of KDM5A by miR-421 in Human Ovarian Cancer Suppresses the Progression of Ovarian Cancer Cells.

作者信息

Ren Fang, Shrestha Christina, Shi Huirong, Sun Fangfang, Zhang Minghui, Cao Yuan, Li Gailing

机构信息

Department of Gynecology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Sep 23;13:9419-9428. doi: 10.2147/OTT.S266211. eCollection 2020.

DOI:10.2147/OTT.S266211
PMID:33061428
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7520141/
Abstract

PURPOSE

The retinoblastoma binding protein RBP2 (KDM5A) is a histone demethylase that promotes cell growth in many human cancers. A series of functional experiments were conducted to explore the role of miR-421/KDM5A in ovarian cancer cells and their underlying molecular mechanisms.

MATERIALS AND METHODS

Public microarray databases were analyzed to assess KDM5A and miR-421 expression in ovarian cancer. KDM5A was predicted to be a target of miR-421 using software analysis. The expression of the miR-421/KDM5A regulatory axis in ovarian cancer and the mechanisms of its effects on proliferation, migration, and invasion of ovarian cancer cell lines were investigated.

RESULTS

Compared with normal ovarian tissues, the expression of KDM5A mRNA and protein was elevated (P<0.05), and miR-421 expression was reduced in ovarian cancer tissue (P<0.05). miR-421 was found to bind specifically to the KDM5A gene. Silencing KDM5A or overexpressing miR-421 significantly inhibited proliferation, migration, and invasion of OVCAR-8 and SKOV-3 cells. Similarly, compared with nude mice injected with cells transfected with empty capsids, the in vivo proliferation rate of OVCAR-8 cells after miR-421 overexpression was reduced significantly.

CONCLUSION

The miR-421/KDM5A regulatory axis plays an important role in the development and progression of ovarian cancer cells.

摘要

目的

视网膜母细胞瘤结合蛋白RBP2（KDM5A）是一种组蛋白去甲基化酶，在多种人类癌症中促进细胞生长。进行了一系列功能实验以探讨miR-421/KDM5A在卵巢癌细胞中的作用及其潜在分子机制。

材料与方法

分析公共微阵列数据库以评估KDM5A和miR-421在卵巢癌中的表达。使用软件分析预测KDM5A是miR-421的靶标。研究了miR-421/KDM5A调控轴在卵巢癌中的表达及其对卵巢癌细胞系增殖、迁移和侵袭的影响机制。

结果

与正常卵巢组织相比，卵巢癌组织中KDM5A mRNA和蛋白的表达升高（P<0.05），而miR-421表达降低（P<0.05）。发现miR-421特异性结合KDM5A基因。沉默KDM5A或过表达miR-421可显著抑制OVCAR-8和SKOV-3细胞的增殖、迁移和侵袭。同样，与注射空衣壳转染细胞的裸鼠相比，miR-421过表达后OVCAR-8细胞的体内增殖率显著降低。

结论

miR-421/KDM5A调控轴在卵巢癌细胞的发生和发展中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc10/7520141/3c4a0468a9db/OTT-13-9419-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc10/7520141/539b3f8c0f9d/OTT-13-9419-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc10/7520141/e9fd334a1727/OTT-13-9419-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc10/7520141/4c173cd1fb37/OTT-13-9419-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc10/7520141/ce3b81f6e603/OTT-13-9419-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc10/7520141/3c4a0468a9db/OTT-13-9419-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc10/7520141/539b3f8c0f9d/OTT-13-9419-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc10/7520141/e9fd334a1727/OTT-13-9419-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc10/7520141/4c173cd1fb37/OTT-13-9419-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc10/7520141/ce3b81f6e603/OTT-13-9419-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc10/7520141/3c4a0468a9db/OTT-13-9419-g0005.jpg

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