Research Paper Volume 11, Issue 22 pp 9982—9999

Circular RNA hsa_circ_0000515 acts as a miR-326 sponge to promote cervical cancer progression through up-regulation of ELK1

Qiu Tang 1, *, , Zhigang Chen 1, *, , Liangping Zhao 2, , Hai Xu 3, ,

  • 1 Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China
  • 2 Department of Gynecology and Obstetrics, Wuhan Central Hospital, Wuhan 430014, China
  • 3 Department of Obstetrics and Gynecology, Huangjiahu Hospital, Hubei University of Chinese Medicine, Wuhan 430065, China
* Co-first authors

received: March 30, 2019 ; accepted: October 3, 2019 ; published: November 26, 2019 ;

https://doi.org/10.18632/aging.102356
How to Cite
This article has been corrected. See Correction. Aging (Albany NY). 2020 Feb 10. https://doi.org/10.18632/aging.102853 [Epub ahead of print]

Copyright © 2019 Tang 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

This study investigates the role of circular RNA (circRNA) hsa_circ_0000515 in cervical cancer and the underlying mechanism associated with microRNA-326 (miR-326). hsa_circ_0000515 and ETS transcription factor ELK1 (ELK1) were initially over-expressed and miR-326 was down-regulated in cervical cancer tissues and cells. Low hsa_circ_0000515 expression was found to be associated with favorable prognosis of patients with cervical cancer. A series of mimics, inhibitors, over-expression plasmids or siRNAs were introduced into cervical cancer cells to alter the expression of hsa_circ_0000515, miR-326 and ELK1. In vitro experiments exhibited that silencing of hsa_circ_0000515 or upregulation of miR-326 resulted in suppressed proliferation and invasion, along with induced apoptosis and autophagy of cervical cancer cells. Dual-luciferase reporter assay, RNA pull-down and RIP assays highlighted that hsa_circ_0000515 was able to act as a ceRNA of miR-326 to increase ELK1. Furthermore, enhancement of ELK1 expression resulted in enhanced proliferation and invasion but repressed apoptosis and autophagy of cervical cancer cells. In vivo experiments further confirmed the suppressed tumor growth by hsa_circ_0000515 silencing. Our findings demonstrated that hsa_circ_0000515 acts as a tumor promoter in cervical cancer. The study provides evidence for targeting hsa_circ_0000515 for therapeutic purposes in treating cervical cancer.

Abbreviations

circRNAs: circular RNAs; ceRNA: competing endogenous RNAs; TCF: ternary complex factor; GEO: gene expression omnibus.