Research Paper Volume 11, Issue 17 pp 6805—6838

Long non-coding RNA, HOTAIRM1, promotes glioma malignancy by forming a ceRNA network

Qingyu Liang 1, , Xue Li 1, , Gefei Guan 1, , Xiaoyan Xu 2, , Chen Chen 3, , Peng Cheng 1, , Wen Cheng 1, , Anhua Wu 1, ,

  • 1 Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
  • 2 Department of Pathophysiology, College of Basic Medicine Science, China Medical University, Shenyang, Liaoning Province, China
  • 3 The Research Center for Medical Genomics, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Life Sciences, China Medical University, Shenyang, Liaoning Province, China

received: April 30, 2019 ; accepted: August 12, 2019 ; published: September 2, 2019 ;

https://doi.org/10.18632/aging.102205
How to Cite

Copyright © 2019 Liang 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 play critical roles in tumorigenesis and the immune process. In this study, RNA sequencing data for 946 glioma samples from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas databases were analyzed to evaluate the prognostic value and function of homeobox A transcript antisense RNA myeloid-specific (HOTAIRM)1. HOTAIRM1 expression was associated with clinical and molecular features of glioma: patients with high HOTAIRM1 expression were more likely to be classified as malignant cases, and elevated HOTAIRM1 level was associated with shorter survival time in subgroups stratified by clinical and molecular features. A multivariate Cox regression analysis showed that HOTAIRM1 was an independent prognostic factor for patient outcome. In vitro experiments revealed that HOTAIRM1 knockdown suppressed the malignant behavior of glioma and increased tumor sensitivity to temozolomide. The results of an in silico analysis indicated that HOTAIRM1 promotes the malignancy of glioma by acting as a sponge for microRNA (miR)-129-5p and miR-495-3p. HOTAIRM1 overexpression was also associated with immune activation characterized by enhanced T cell-mediated immune and inflammatory responses. These results suggest that HOTAIRM1 is a prognostic biomarker and potential therapeutic target in glioma.

Abbreviations

ATRX: alpha thalassemia/mental retardation syndrome X-linked; CCK-8: Cell Counting Kit-8; ceRNA: competing endogenous RNA; CGGA: Chinese Glioma Genome Atlas; DEG: differentially expressed gene; DGC: differentiated glioblastoma cell; DMEM: Dulbecco’s Modified Eagle’s Medium; EGFR: epidermal growth factor receptor; EMT: epithelial–mesenchymal transition; FBS: fetal bovine serum; IDH: isocitrate dehydrogenase; GBM: glioblastoma multiforme; GBM-IDHwt: GBM with wild-type IDH; GO: Gene Ontology; GSEA: gene set enrichment analysis; high-exp: high expression of HOTAIRM1; HOTAIRM1: homeobox A transcript antisense RNA myeloid-specific 1; HR: hazard ratio; IGFBP3: insulin-like growth factor-binding protein 3; KPS: Karnofsky performance score; LGG: low-grade glioma; LGG-IDHwt: low-grade glioma with wild-type IDH; lncRNA: long non-coding RNA; low-exp: low expression of HOTAIRM1; MGMT: O-6-methylguanine-DNA methyltransferase; MCODE: Molecular Complex Detection; miRNA: microRNA; OS: overall survival; PCA: principal component analysis; PPI: protein–protein interaction; PTEN: phosphatase and tensin homolog; qRT-PCR: quantitative real-time polymerase chain reaction; siRNA: small interfering RNA; SOD2: superoxide dismutase; SPP1: secreted phosphoprotein 1; TCGA: The Cancer Genome Atlas; TME: tumor microenvironment; TMZ: temozolomide; Treg: regulatory T cell; up-DEG: differentially upregulated gene; WHO: World Health Organization.