MiR-30a-5p Suppresses Tumor Metastasis of Human Colorectal Cancer by Targeting ITGB3

Cell Physiol Biochem. 2016;39(3):1165-76. doi: 10.1159/000447823. Epub 2016 Aug 31.

Abstract

Aims: MicroRNAs (miRNAs) are dysregulated in a wide range of malignant diseases, confirming their crucial role in tumor metastasis. MiRNA-30a-5p, a member of the miR-30 family, has been implicated in many types of cancers, including colorectal cancer, a leading cause of death worldwide.

Methods: qRT-PCR, Western blot, Transwell assay,luciferase reporter assay were performed in the present study.

Results: In this study, miR-30a-5p was found to be significantly downregulated in human colorectal cancer tissue specimens and cell lines compared with non-cancerous tissues and cells. The overexpression of miR-30a-5p inhibited the migratory and invasive abilities of colorectal cancer cells and suppressed the epithelial-mesenchymal transition, a crucial process in metastasis. Bioinformatic algorithms and luciferase reporter assays revealed that integrin β3 (ITGB3) is a direct target of miR-30a-5p. Importantly, overexpression of ITGB3 in colorectal cancer cells rescued these cells from miR-30a-5p-mediated suppression of metastasis and restored the epithelial-mesenchymal transition.

Conclusion: Taken together, our study provides the first evidence that miR-30a-5p suppresses colon cancer metastasis through the inhibition of ITGB3. Thus, targeting miR-30a-5p might serve as a promising therapeutic strategy for the treatment of colorectal cancer.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • HEK293 Cells
  • Humans
  • Integrin beta3 / genetics*
  • Integrin beta3 / metabolism
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Signal Transduction
  • Splenic Neoplasms / genetics*
  • Splenic Neoplasms / metabolism
  • Splenic Neoplasms / pathology

Substances

  • ITGB3 protein, human
  • Integrin beta3
  • MIRN30b microRNA, human
  • MicroRNAs
  • Luciferases