Research Paper Volume 11, Issue 11 pp 3811—3823
Long non-coding RNA AGAP2-AS1 exerts oncogenic properties in glioblastoma by epigenetically silencing TFPI2 through EZH2 and LSD1
- 1 Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, P.R. China
- 2 Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, P.R. China
Received: March 12, 2019 Accepted: June 3, 2019 Published: June 11, 2019
https://doi.org/10.18632/aging.102018How to Cite
Copyright: Luo 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
Long non-coding RNAs (LncRNAs) have attracted increasing attention for their important regulation functions in a wide range of malignancies. AGAP2-AS1 was demonstrated as an oncogene in several cancers, including glioblastoma (GBM). However, the biological mechanisms of AGAP2-AS1 in GBM progression are still unclear. Herein, we found that AGAP2-AS1 expression was up-regulated in GBM tissues and cells. High AGAP2-AS1 expression may predict a poor prognosis in GBM patients. Functionally, silencing of AGAP2-AS1 suppressed proliferation and invasion, while enhanced apoptosis in GBM cells. Overexpression of AGAP2-AS1 promoted cell proliferation and invasion. Mechanically, AGAP2-AS1 could interact with EZH2 and LSD1, recruiting them to TFPI2 promoter region to inhibit its transcription. Moreover, TFPI2 overexpression decreased proliferation and invasion, and facilitated apoptosis in GBM cells. Furthermore, the tumor-suppressive effects mediated by AGAP2-AS1 knockdown were greatly reversed following down-regulation of TFPI2. Also, suppression of AGAP2-AS1 impaired tumor growth of GBM in vivo. In summary, AGAP2-AS1 exerts oncogenic functions in GBM by epigenetically silencing TFPI2 expression through binding to EZH2 and LSD1, illuminating a novel mechanism of AGAP2-AS1 in GBM development and furnishing a prospective therapeutic method to combat GBM.
Abbreviations
lncRNAs: Long non-coding RNAs; EZH2: Enhancer of zeste homolog 2; LSD1: lysine-specific demethylase 1; PRC2: polycomb repressive complex 2; H3K27me3: histone H3 lysine 27 trimethylation; H3K4me2: histone 3 lysine 4 demethylation; NSCLC: non-small cell lung cancer; NHA: normal human astrocytes; GBM: glioblastoma; EdU: 5-ethynyl-2′-deoxyuridine; siRNAs: small interference RNAs; RIP: RNA immunoprecipitation; ChIP: chromatin immunoprecipitation; TFPI2: tissue factor pathway inhibitor 2; CBP: CREB-binding protein.