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microRNA-4500 inhibits human glioma cell progression by targeting IGF2BP1

Zheng-Wei Li1, Min Xue2, Bing-Xin Zhu1

  • 1Neurosurgery Department, Xuzhou Children's Hospital, Xuzhou Medical University, Xuzhou, China.

Biochemical and Biophysical Research Communications
|April 20, 2019
PubMed

Insights

MicroRNA-4500 (miR-4500) suppresses glioma progression by targeting Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1). Lower miR-4500 levels in glioma tissues correlate with higher IGF2BP1, confirming its role in tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Overexpression of Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is linked to glioma cell progression.
  • MicroRNAs (miRNAs) represent a potential therapeutic strategy for silencing oncogenes like IGF2BP1.

Purpose of the Study:

  • To investigate the potential of microRNA-4500 (miR-4500) to silence IGF2BP1 in glioma cells.
  • To elucidate the role of the miR-4500/IGF2BP1 axis in glioma cell behavior and its clinical relevance.

Main Methods:

  • Bioinformatic analysis to predict miR-4500 targeting of IGF2BP1 3'-untranslated region (3'-UTR).
  • In vitro experiments involving ectopic miR-4500 overexpression and inhibition in A172 and primary human glioma cells.
  • CRISPR/Cas9 gene editing to knock out IGF2BP1 in A172 cells.
  • Analysis of IGF2BP1 and its target genes (Gli1, IGF2, c-Myc) expression.
  • Assessment of glioma cell proliferation, survival, migration, and invasion.
  • Correlation analysis of miR-4500 and IGF2BP1 levels in human glioma tissues.

Main Results:

  • Bioinformatic analysis confirmed miR-4500's putative targeting of the IGF2BP1 3'-UTR.
  • Ectopic overexpression of wild-type miR-4500 (but not mutant) downregulated IGF2BP1 and its targets (Gli1, IGF2, c-Myc) in glioma cells.
  • miR-4500 overexpression inhibited glioma cell growth, survival, proliferation, migration, and invasion.
  • miR-4500 inhibition increased IGF2BP1 expression and promoted glioma cell progression.
  • IGF2BP1 knockout inhibited A172 cell progression, and miR-4500's effects were abolished in these cells.
  • Human glioma tissues showed downregulated miR-4500 and upregulated IGF2BP1.

Conclusions:

  • miR-4500 functions as a tumor suppressor in human glioma by directly targeting and downregulating IGF2BP1.
  • The miR-4500/IGF2BP1 axis is a critical regulator of glioma cell progression.
  • miR-4500 represents a potential therapeutic target for glioma treatment.
Keywords:
Gli1GliomaIGF2BP1c-MycmicroRNA-4500

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