Long Non-coding RNA COX10-AS1 Promotes Glioma Progression by Competitively Binding miR-1-3p to Regulate ORC6 Expression

Neuroscience. 2024 Mar 5:540:68-76. doi: 10.1016/j.neuroscience.2023.09.020. Epub 2024 Jan 18.

Abstract

Glioma is one of the most common and difficult to cure malignant primary tumors of the central nervous system. Long non-coding RNA (lncRNA) has been reported to play important functions in biological processes of many tumors, including glioma. In our study, we aimed to reveal the role and molecular mechanisms of lncRNA COX10-AS1 in regulating the progression of glioma. First of all, we showed that lncRNA COX10-AS1 was significantly increased in glioma tissues and cell lines, and high-expressed COX10-AS1 was associated with a poor prognosis in glioma patients. Moreover, through performing the functional experiments, including CCK-8, colony formation and Transwell assays, we confirmed that COX10-AS1 ablation curbed cell proliferation, migration and invasion in glioblastoma (GBM) cells. In addition, we uncovered that there existed a regulatory relationship that COX10-AS1 upregulated OCR6 by sponging miR-1-3p in GBM cells, and the following rescue assays demonstrated that both miR-1-3p downregulation and origin recognition complex subunit 6 (ORC6) overexpression rescued cell viability, migration and invasion in the COX10-AS1-deficient GBM cells. Consistently, we also verified that COX10-AS1 promoted tumorigenesis of the GBM cells in vivo through modulating the miR-1-3p/ORC6 axis. On the whole, our findings indicated a novel ceRNA pattern in which COX10-AS1 elevated OCR6 expression via sponging miR-1-3p, therefore boosting tumorigenesis in glioma, and we firstly discussed the underlying mechanisms by which the COX10-AS1/miR-1-3p/ORC6 axis affected the progression of glioma.

Keywords: COX10-AS1; ORC6; glioma; long non-coding RNA; miR-1-3p.

MeSH terms

  • Alkyl and Aryl Transferases* / genetics
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Electron Transport Complex IV / metabolism
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma* / genetics
  • Glioma* / genetics
  • Glioma* / pathology
  • Humans
  • Membrane Proteins / genetics
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Origin Recognition Complex / genetics
  • Origin Recognition Complex / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • Origin Recognition Complex
  • ORC6 protein, human
  • COX10 protein, human
  • Electron Transport Complex IV
  • Membrane Proteins
  • Alkyl and Aryl Transferases
  • MIRN1 microRNA, human