Long noncoding RNA FOXD2-AS1 promotes glioma cell cycle progression and proliferation through the FOXD2-AS1/miR-31/CDK1 pathway

J Cell Biochem. 2019 Dec;120(12):19784-19795. doi: 10.1002/jcb.29284. Epub 2019 Jul 26.

Abstract

Long noncoding RNAs (lncRNAs) are vital mediators involved in cancer progression. Previous studies confirmed that FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is upregulated in tumor diseases. The potential influence of FOXD2-AS1 in glioma progression, however, remains unknown. In this paper, FOXD2-AS1 was found to be upregulated in glioma tissues. Its level was linked with glioma stage. Moreover, glioma patients expressing high level of FOXD2-AS1 suffered worse prognosis. Biological functions of FOXD2-AS1 in glioma cells were analyzed through integrative bioinformatics and TCGA RNA sequencing data analysis. Pathway enrichment analysis uncovered that FOXD2-AS1 was mainly linked with cell cycle regulation in both low-grade glioma and glioblastoma. Further experiments demonstrated that silence of FOXD2-AS1 inhibited proliferation, arrested cell cycle and downregulated cyclin-dependent kinase 1 (CDK1) in human glioma cells. Dual-luciferase reporter assay confirmed that FOXD2-AS1 upregulated CDK1 by sponging miR-31. Rescue assays were performed and confirmed the regulatory loop FOXD2-AS1/miR-31/CDK1 in glioma. Collectively, our results indicated that the FOXD2-AS1/miR-31/CDK1 axis influenced glioma progression, providing a potential new target for glioma patients.

Keywords: FOXD2-AS1; G1 phase arrest; cyclin-dependent kinase 1; glioblastoma; long noncoding RNA; miR-31; proliferation.

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology*
  • CDC2 Protein Kinase / genetics*
  • CDC2 Protein Kinase / metabolism
  • Case-Control Studies
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / genetics
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Glioma / genetics
  • Glioma / mortality
  • Glioma / pathology*
  • Humans
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Survival Analysis

Substances

  • MIRN31 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA FOXD2-AS1, human
  • CDC2 Protein Kinase
  • CDK1 protein, human