MiR-433-3p suppresses cell growth and enhances chemosensitivity by targeting CREB in human glioma

Oncotarget. 2017 Jan 17;8(3):5057-5068. doi: 10.18632/oncotarget.13789.

Abstract

Previous studies reported that miR-433 exerts function widely in human tumorigenesis and development. Here, we further investigate the potential role of miR-433 in glioma. Quantitative real-time PCR demonstrated that miR-433-3p and miR-433-5p were low expressed in glioma tissues and cell lines. Functional studies suggested that the overexpression of miR-433-3p suppressed proliferation, induced apoptosis and inhibited invasion and migration of human glioma cells. But the growth and metastasis of glioma cells were not significantly influenced by overexpression of miR-433-5p. In a xenograft model, we also showed that miR-433-3p had an inhibitory effect on the growth of glioma. Bioinformatics coupled with luciferase and western blot assays revealed that CREB is a direct target of miR-433-3p, and the overexpression of CREB can rescue the phenotype changes induced by miR-433-3p overexpression. Besides, miR-433-3p could increase chemosensitivity of glioma to temozolomide by targeting CREB in vitro and in vivo. Taken together, these results suggest that miR-433-3p may function as a potential marker in diagnostic and therapeutic target for glioma.

Keywords: CREB; carcinogenesis; chemosensitivity; glioma; miR-433-3p.

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / pharmacology
  • Down-Regulation
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / drug therapy
  • Glioma / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Temozolomide
  • Young Adult

Substances

  • 3' Untranslated Regions
  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • MIRN433 microRNA, human
  • MicroRNAs
  • Dacarbazine
  • Temozolomide