Linc00152 promotes malignant progression of glioma stem cells by regulating miR-103a-3p/FEZF1/CDC25A pathway

Mol Cancer. 2017 Jun 26;16(1):110. doi: 10.1186/s12943-017-0677-9.

Abstract

Background: Glioma is one of the most frequent intracranial malignant tumors. LncRNAs have been identified as new modulators in the origination and progression of glioma.

Methods: Quantitative real-time PCR were conducted to evaluate the expression of linc00152 and miRNA-103a-3p in glioma tissues and cells. Western blot were used to determine the expression of FEZF1 and CDC25A in glioma tissues and cells. Stable knockdown of linc00152 or over-expression of miR-103a-3p in glioma stem cells (GSCs) were established to explore the function of linc00152 and miR-103a-3p in GSCs. Further, luciferase reports were used to investigate the correlation between linc00152 and miR-103a-3p. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate the function of linc00152 and miR-103a-3p in GSC malignant biological behaviors. ChIP assays were employed to ascertain the correlations between FEZF1 and CDC25A.

Results: Linc00152 was up-regulated in glioma tissues as well as in GSCs. Knockdown of linc00152 inhibited cell proliferation, migration and invasion, while promoted GSC apoptosis. Linc00152 regulated the malignant behavior of GSCs by binding to miR-103a-3p, which functions as a tumor suppressor. In addition, knockdown of linc00152 down-regulated forebrain embryonic zinc finger protein 1 (FEZF1), a direct target of miR-103a-3p which played an oncogenic role in GSCs. FEZF1 elevated promoter activities and up-regulated expression of the oncogenic gene cell division cycle 25A (CDC25A). CDC25A over-expression activated the PI3K/AKT pathways, which regulated the malignant behavior of GSCs.

Conclusions: Linc00152/miR-103a-3p/FEZF1/CDC25A axis plays a novel role in regulating the malignant behavior of GSCs, which may be a new potential therapeutic strategy for glioma therapy.

Keywords: CDC25A; FEZF1; Glioma stem cells; Long non-coding RNA; linc00152; miR-103a-3p.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Apoptosis / genetics
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Glioma / genetics
  • Glioma / pathology*
  • Humans
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplastic Stem Cells / pathology*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / genetics*
  • Repressor Proteins
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • cdc25 Phosphatases / genetics
  • cdc25 Phosphatases / metabolism

Substances

  • 3' Untranslated Regions
  • FEZF1 protein, human
  • MIRN103 microRNA, human
  • MIRN103A2 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Repressor Proteins
  • Transcription Factors
  • long non-coding RNA Linc00152, human
  • Proto-Oncogene Proteins c-akt
  • CDC25A protein, human
  • cdc25 Phosphatases