MicroRNA-3607 inhibits the tumorigenesis of colorectal cancer by targeting DDI2 and regulating the DNA damage repair pathway

Apoptosis. 2019 Aug;24(7-8):662-672. doi: 10.1007/s10495-019-01549-5.

Abstract

Mutations in the DNA damage repair (DDR) pathway are frequently detected in colorectal cancer (CRC). The dysregulation of miRNAs, such as oncogenes or tumor suppressors, participates in CRC tumorigenesis. A previous study showed that low miR-3607 expression correlated with poor survival in prostate cancer patients, but its role in CRC remains unclear. In this study, we analyzed miR-3607 expression Pan-Cancer data from the NCI's Genomic Data Commons (GDC) and found that miR-3607 was downregulated in lymphatic invasion patients and in recurrent cancer and correlated with Pan-Cancer patient survival. Functional studies indicated that the overexpression of miR-3607 decreased CRC cell proliferation, migration and invasion. Additionally, we used gene set enrichment analysis (GSEA), Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and a protein-protein interaction network to demonstrate that miR-3607 affects the DDR pathway. Luciferase reporter and apoptosis assays confirmed that DNA damage inducible 1 homolog 2 (DDI2) is the functional target of miR-3607. Therefore, miR-3607 inhibits the tumorigenesis of CRC probably by suppressing the oncogene DDI2, and it might serve as a novel target for CRC prediction and therapy.

Keywords: Apoptosis; Colorectal cancer; DDI2; DNA damage repair pathway; MiR-3607.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Aspartic Acid Proteases / antagonists & inhibitors
  • Aspartic Acid Proteases / genetics*
  • Aspartic Acid Proteases / metabolism
  • Binding Sites
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • DNA Damage / genetics*
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Mutation
  • Neoplasm Invasiveness
  • Protein Interaction Maps

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • Aspartic Acid Proteases
  • DDI2 protein, human