MicroRNA-150 inhibits the proliferation and metastasis potential of colorectal cancer cells by targeting iASPP

Oncol Rep. 2018 Jul;40(1):252-260. doi: 10.3892/or.2018.6406. Epub 2018 Apr 30.

Abstract

In the present study, the function of miR-150 and its downstream target iASPP in the growth and metastasis of colorectal cancer (CRC) cells was investigated. The expression of miR-150 and iASPP was first investigated in clinical CRC samples. Subsequently, the effects of miR-150 overexpression and iASPP inhibition on cell viability, cell cycle distribution, apoptosis, migration and invasion were detected with CCK-8, flow cytometry, scratch and Transwell assays. The interaction between miR-150 and iASPP was confirmed using a dual-luciferase assay. Subsequently, the key role of iASPP in the anti-CRC function of miR-150 was assessed by inducing the expression of the gene in miR-150 overexpressed SW480 cells. In clinical samples, the level of miR-150 was downregulated, while iASPP was induced. Enforced expression of miR-150 decreased the viability, induced G1 cell cycle arrest and apoptosis, and inhibited the migration and invasion of SW480 cells. Knockdown of iASPP exerted a similar effect on SW480 cells to that of the overexpression of miR-150. Dual-luciferase assay demonstrated that miR-150 directly bound to iASPP and inhibited its transcription. The function of miR-150 depended on the inhibition of iASPP; induced expression of iASPP in miR-150-knockdown SW480 and HCT116 cells restored cell viability, migration and invasion while inhibiting G1 cell cycle arrest and apoptosis. Increased expression of miR-150 suppressed viability, proliferation, migration and invasion of SW480 cells. Furthermore, iASPP was a direct target of miR-150 and played a key role in its anti-CRC function. miR-150 may be a promising predictor of prognosis in CRC patients.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics*
  • Cell Cycle Checkpoints / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HCT116 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / genetics*
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis
  • Prognosis
  • Protein Binding / genetics
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics*

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • MIRN150 microRNA, human
  • MicroRNAs
  • PPP1R13L protein, human
  • Repressor Proteins