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Research Paper|Volume 12, Issue 1|pp 318—339

Circ-EPB41L5 regulates the host gene EPB41L5 via sponging miR-19a to repress glioblastoma tumorigenesis

Tao Lv1, Yifeng Miao2, Tianqi Xu1, Wenhua Sun2, Youzhou Sang3, Feng Jia1, Xiaohua Zhang1
  • 1Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
  • 2Department of Neurosurgery, Ren Ji Hospital South Campus, School of Medicine, Shanghai Jiao Tong University, Shanghai 201112, China
  • 3State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
* Co-first authors
Received: September 3, 2019Accepted: December 5, 2019Published: January 6, 2020
https://doi.org/10.18632/aging.102617

Copyright: © 2020 Lv 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

Background: Circular RNAs (circRNAs) are widely expressed non-coding RNAs in eukaryotic cells, involved in regulating tumorigenesis of several types of cancers. However, the expression profiles and the precise functional role in glioblastoma remain unclear.

Results: Circ-EPB41L5 was downregulated in glioblastoma tissues and cell lines compared to the normal brain tissues and cell lines. Low circ-EPB41L5 expression was correlated to the poor prognosis of glioblastoma patients, while the overexpression inhibited proliferation, clone formation, migration, and invasion abilities of glioma cells, and the suppression had counter effects. Furthermore, RNA-seq results determined that the host gene was the target gene of circ-EPB41L5, which served as a sponge against miR-19a and inhibited miR-19a activity from upregulating the expression of EPB41L5. Finally, we found that circ-EPB41L5 regulated the RhoC expression and phosphorylation of AKT through EPB41L5.

Conclusion: The current study highlights a novel suppressive function of circ-EPB41L5 and reveals that circ-EPB41L5/miR-19a/EPB41L5/p-AKT regulatory axis plays a striking role in the progression of glioblastoma, which provides a novel insight into the mechanisms underlying glioblastoma.

Methods: The expression profiles of circRNAs in glioblastoma were determined by Illumina HiSeq from six glioblastoma tissues and six normal brain tissues. Then, the correlation between circ-EPB41L5 expression and clinical features and the survival time of 45 glioblastoma patients was detected. The interaction between circ-EPB41L5, miR-19a, and EPB41L5 was assessed by luciferase reporter and RNA pull-down assays. The effects of expression of the ectopic intervention of circ-EPB41L5 or EPB41L5 on proliferation, clone formation, migration, and invasion in vitro and tumorigenesis in vivo were observed to evaluate the function of circ-EPB41L5 or EPB41L5.