Long noncoding RNA DLX6-AS1 accelerates the glioma carcinogenesis by competing endogenous sponging miR-197-5p to relieve E2F1

Gene. 2019 Feb 20:686:1-7. doi: 10.1016/j.gene.2018.10.065. Epub 2018 Oct 23.

Abstract

Long noncoding RNAs (lncRNAs) participate in numerous of human cancer tumorigenesis. Nevertheless, the in-depth molecular mechanism that lncRNAs regulate the gliomagenesis is still ambiguous. In this research, our study invests energy in the biologic roles of lncRNA DLX6-AS1 on the glioma tumorigenesis. Here, we demonstrated that DLX6-AS1 expression was both high-expressed in the glioma cells and tissue, and the overexpression of DLX6-AS1 was clinically correlated with the poor outcome of glioma patients. In the cellular functional assays, silenced DLX6-AS1 expression by siRNAs inhibited the proliferation, invasion and tumor growth in vitro and in vivo, while the enhanced DLX6-AS1 expression by plasmids promotes them. The bioinformatics predictive tools, luciferase reporter assay and correlation analysis found that miR-197-5p could both target the 3'-UTR of DLX6-AS1 as well as E2F1 gene, constructing DLX6-AS1-miR-197-5p-E2F1 axis. Moreover, receiver operating characteristic (ROC) curve analysis revealed that lncRNA DLX6-AS1 has valuable diagnostic value clinical diagnose for the glioma patients (AUC = 0.736). Overall, our finding supports that DLX6-AS1 accelerates the glioma carcinogenesis by competing endogenous sponging miR-197-5p to relieve E2F1, acting as a novel therapeutic target for glioma.

Keywords: DLX6-AS1; E2F1; Glioma; Long noncoding RNA; miR-197-5p.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • E2F1 Transcription Factor / biosynthesis*
  • E2F1 Transcription Factor / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics

Substances

  • E2F1 Transcription Factor
  • E2F1 protein, human
  • MIRN197 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Long Noncoding
  • RNA, Neoplasm