Interplay between PCBP2 and miRNA modulates ARHGDIA expression and function in glioma migration and invasion

Oncotarget. 2016 Apr 12;7(15):19483-98. doi: 10.18632/oncotarget.6869.

Abstract

RNA-RNA and protein-RNA interactions are essential for post-transcriptional regulation in normal development and may be deregulated in cancer initiation and progression. The RNA-binding protein PCBP2, an oncogenic protein in human malignant gliomas, is an essential regulator of mRNA and miRNA biogenesis, stability and activity. Here, we identified Rho GDP dissociation inhibitor α (ARHGDIA) as a target mRNA that binds to PCBP2, and we uncovered the role of ARHGDIA as a putative metastasis suppressor through analyses of in vitro and in vivo models of EMT and metastasis. Furthermore, we demonstrated that ARHGDIA is a potential target of miR-151-5p and miR-16 in gliomas. The interaction between PCBP2 and the 3'UTR of the ARHGDIA mRNA may induce a local change in RNA structure that favors subsequent binding of miR-151-5p and miR-16, thus leading to the suppression of ARHGDIA expression. PCBP2 may facilitate miR-151-5p and miR-16 promotion of glioma cell migration and invasion through mitigating the function of ARHGDIA.

Keywords: ARHGDIA; PCBP2; glioma; miRNA; migration and invasion.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adult
  • Aged
  • Animals
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • HeLa Cells
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Protein Binding
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Transplantation, Heterologous
  • Young Adult
  • rho Guanine Nucleotide Dissociation Inhibitor alpha / genetics*
  • rho Guanine Nucleotide Dissociation Inhibitor alpha / metabolism

Substances

  • 3' Untranslated Regions
  • ARHGDIA protein, human
  • MIRN151a microRNA, human
  • MIRN16 microRNA, human
  • MicroRNAs
  • PCBP2 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • rho Guanine Nucleotide Dissociation Inhibitor alpha