MiR-181a/b induce the growth, invasion, and metastasis of neuroblastoma cells through targeting ABI1

Mol Carcinog. 2018 Sep;57(9):1237-1250. doi: 10.1002/mc.22839. Epub 2018 Jun 16.

Abstract

Neuroblastoma is a pediatric malignancy, and the clinical phenotypes range from localized tumors with excellent outcomes to widely metastatic disease in which long-term survival is approximately 40%, despite intensive therapy. Emerging evidence suggests that aberrant miRNA regulation plays a role in neuroblastoma, but the miRNA functions and mechanisms remain unknown. miR-181 family members were detected in 32 neuroblastoma patients, and the effects of miR-181a/b on cell viability, invasion, and migration were evaluated in vitro and in vivo. A parallel global mRNA expression profile was obtained for neuroblastoma cells overexpressing miR-181a. The potential targets of miR-181a/b were validated. miR-181a/b expression levels were positively associated with MYCN amplification and neuroblastoma aggressiveness. Moreover, ectopic miR-181a/b expression significantly induced the growth and invasion of neuroblastoma cells in vitro and in vivo. Microarray analysis revealed that mRNAs were consistently downregulated after miR-181a overexpression, leading to cell migration. In addition, the expression of ABI1 was suppressed by miR-181a/b, and ABI1 was validated as a direct target of miR-181a/b. We concluded that miR-181a/b were significantly upregulated in aggressive neuroblastoma, which enhanced its tumorigenesis and progression by suppressing the expression of ABI1.

Keywords: abl interactor1; miR-181a; miR-181b; microarray; migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cytoskeletal Proteins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology

Substances

  • ABI1 protein, human
  • Abi1 protein, mouse
  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • MIrn181 microRNA, human
  • MicroRNAs
  • mirn181 microRNA, mouse