Diphthamide Biosynthesis 1 is a Novel Oncogene in Colorectal Cancer Cells and is Regulated by MiR-218-5p

Cell Physiol Biochem. 2017;44(2):505-514. doi: 10.1159/000485087. Epub 2017 Nov 17.

Abstract

Background/aims: This study focused on the oncogenic role of Diphthamide biosynthesis 1 (DPH1) in colorectal cancer (CRC) cells.

Methods: The expression of DPH1 was determined by quantitative RT-PCR analysis and western blotting in CRC tissues. The role of DPH1 in CRC cells was investigated via cell viability and invasion assays under the condition of DPH1 silencing or overexpression. Bioinformatics analysis and luciferase reporter analysis were used to identify the upstream microRNA which might regulate DPH1.The inverse correlation between the microRNA and DPH1 was also detected in CRC cells.

Results: We identified an unexpected role for DPH1 as an oncogene in CRC cells. The tumour-suppressive miR-218-5p regulates DPH1 directly and negatively. Loss of miR-218-5p drives the oncogenic role of DPH1 in CRC cells.

Conclusion: The modulation of DPH1 by miR-218-5p may be an important regulatory axis during CRCtumourigenesis.

Keywords: CRC; Dph1; MiR-218-5p; Tumourigenesis.

MeSH terms

  • 3' Untranslated Regions
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Aged
  • Antagomirs / metabolism
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • HT29 Cells
  • Humans
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Sequence Alignment
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • DPH1 protein, human
  • MIRN218 microRNA, human
  • MicroRNAs
  • Minor Histocompatibility Antigens
  • RNA, Small Interfering
  • Tumor Suppressor Proteins