Research Paper Volume 13, Issue 6 pp 8214—8227
Bromodomain-containing protein 4 silencing by microRNA-765 produces anti-ovarian cancer cell activity
- 1 Obstetrics and Gynecology Department, Suzhou Ninth People's Hospital of Soochow University, Suzhou, China
- 2 Obstetrics and Gynecology Department, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, China
Received: December 3, 2020 Accepted: January 14, 2021 Published: March 3, 2021
https://doi.org/10.18632/aging.202632How to Cite
Copyright: © 2021 Ji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Bromodomain-containing protein 4 (BRD4) overexpression promotes ovarian cancer progression, and represents an important therapeutic oncotarget. This current study identified microRNA-765 (miR-765) as a novel BRD4-targeting miRNA. We showed that miR-765 directly associated with and silenced BRD4. In primary ovarian cancer cells and established cell lines (SKOV3 and CaOV3), ectopic overexpression of miR-765 inhibited cancer cell proliferation, migration and invasion, and induced apoptosis activation. In contrast, miR-765 inhibition by its anti-sense induced BRD4 upregulation to promote ovarian cancer cell proliferation, migration and invasion. Significantly, miR-765 overexpression-induced anti-ovarian cancer cell activity was largely attenuated by restoring BRD4 expression through an UTR-null BRD4 construct. Moreover, CRISPR/Cas9-induced BRD4 knockout (KO)inhibited proliferation and activated apoptosis in ovarian cancer cells. BRD4 KO in ovarian cancer cells abolished the functional impact of miR-765. miR-765 expression levels were downregulated in human ovarian cancer tissues and cells, correlating with the upregulation of BRD4 mRNA. Collectively, BRD4 silencing by miR-765produces significant anti-ovarian cancer cell activity. miR-765 could be further tested for its anti-ovarian cancer potential.