Cancer Management and Research (2021-01-01)

Long Non-Coding RNA UBA6-AS1 Promotes the Malignant Properties of Glioblastoma by Competitively Binding to microRNA-760 and Enhancing Homeobox A2 Expression

  • Cheng F,
  • Liu J,
  • Zhang Y,
  • You Q,
  • Chen B,
  • Cheng J,
  • Deng C

Journal volume & issue
Vol. Volume 13
pp. 379 – 392

Abstract

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Feifei Cheng,1 Jiang Liu,1 Yundong Zhang,1 Qiuxiang You,1 Bo Chen,2 Jing Cheng,1 Chunyan Deng1 1Department of Neurology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, People’s Republic of China; 2Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing 401120, People’s Republic of ChinaCorrespondence: Chunyan Deng Email [email protected]: The dysregulation of long non-coding RNAs is a frequent finding in glioblastoma (GBM) and is considered as a crucial mechanism contributing to GBM oncogenesis and progression. The biological roles and underlying mechanisms of action of UBA6 antisense RNA 1 (UBA6-AS1) in GBM have been rarely investigated. Therefore, the aim of the present study was to investigate in detail the role of UBA6-AS1 in the modulation of the malignant properties of GBM and explore the possible underlying mechanism(s).Methods: The expression of UBA6-AS1 in GBM was determined via reverse transcription-quantitative PCR. Cell Counting Kit-8 assay, flow cytometric analysis, Transwell migration and invasion assays, and in vivo tumorigenicity assay were applied to elucidate the biological effects of UBA6-AS1 on GBM cells. The possible biological events associated with UBA6-AS1 were investigated by luciferase reporter, RNA immunoprecipitation (RIP) and rescue assays.Results: UBA6-AS1 was overexpressed in GBM, which was consistent with the data from The Cancer Genome Atlas database. In the case of UBA6-AS1 depletion, GBM cell proliferation, migration and invasion were notably decreased and cell apoptosis was enhanced in vitro. Additionally, knockdown of UBA6-AS1 suppressed the proliferation of GBM cells in vivo. Mechanistically, UBA6-AS1 functioned as a competing endogenous RNA by adsorbing miR-760 and, consequently, upregulating homeobox A2 (HOXA2) expression. Rescue experiments demonstrated that the UBA6-AS1 silencing-mediated regulatory effects on GBM cells were reversed by the decrease of miR-760 or restoration of HOXA2 expression.Conclusion: Therefore, the results of the present study revealed that UBA6-AS1 promoted the malignant progression of GBM via targeting the miR-760/HOXA2 axis, thereby representing a promising effective target for the treatment of GBM.Keywords: UBA6 antisense RNA 1, long non-coding RNA, homeobox A2, glioblastoma

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