Long non-coding RNA ENST01108 promotes carcinogenesis of glioma by acting as a molecular sponge to modulate miR-489

Biomed Pharmacother. 2018 Apr:100:20-28. doi: 10.1016/j.biopha.2018.01.126. Epub 2018 Feb 6.

Abstract

Gliomas are the most common primary malignant tumor in the adult central nervous system with poor prognosis. Exploring novel biomarkers and elucidating underlying molecular mechanisms to provide effective therapeutic methods is in an urgent need. Long noncoding RNAs (lncRNAs) is involved in various human diseases including cancer. However, studies on lncRNAs and gliomas are limited. In this study, we explored the expression patterns of lncRNAs in 4 pairs of glioma samples and adjacent normal tissues via microarray and chose the most up-regulated lncRNA ENST01108 (ENST01108) to further verify its oncogenic role in glioma. Clinical data suggest that ENST01108 is closely associated with the malignant status in glioma. In vitro experiment demonstrated that overexpression of ENST01108 promoted glioma cell proliferation, migration, invasion, EMT process and survival, while knockdown of ENST01108 has an opposite effect, indicating that ENST01108 serves as an oncogenic property in glioma carcinogenesis. Further, we identified miR-489 as a direct target of ENST01108 and ENST01108 negatively regulate miR-489 by act as a sponge. SIK1 is verified as the direct target of miR-489 and it is negatively regulated by miR-489. ENST01108 also positively regulate SIKI and it promotes SIKI expression by suppressing miR-489. Taken together, the reciprocal repression of ENST011081 and miR-489 may be served as potential targets for cancer therapeutics in glioma.

Keywords: ENST01108; Glioma; SIK1; miR-489.

MeSH terms

  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Oncogenes
  • Protein Serine-Threonine Kinases / genetics
  • RNA, Long Noncoding / genetics*

Substances

  • MIRN489 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Protein Serine-Threonine Kinases
  • SIK1 protein, human