Runt-related Transcription Factor 1 (RUNX1T1) Suppresses Colorectal Cancer Cells Through Regulation of Cell Proliferation and Chemotherapeutic Drug Resistance

Anticancer Res. 2016 Oct;36(10):5257-5263. doi: 10.21873/anticanres.11096.

Abstract

Background/aim: Altered expression of runt-related transcription factor 1 (RUNX1T1) has been observed in several human cancer types; however, the exact role for RUNX1T1 in colorectal cancer (CRC) remains unclear.

Materials and methods: The GSE21510 CRC and our previously published datasets were utilized in this study. Gene-expression profiling was conducted using the Agilent microarray platform, while data normalization and bioinformatics were conducted using GeneSpring software. AlamarBlue assay was used to assess cell viability in vitro.

Results: The expression of RUNX1T1 was severely down-regulated in primary CRC and cell lines. Lentiviral-mediated re-expression of RUNX1T1 inhibited CRC cell growth, and global gene-expression analysis revealed the cell cycle, DNA replication, and DNA damage as the pathways most affected by RUNX1T1. Forced expression of RUNX1T1 induced a significant reduction in cellular proliferation and sensitized CRC cells to 5-flurouracil.

Conclusion: Our data revealed a novel role for RUNX1T1 as a tumor-suppressor gene in CRC through modulation of multiple cellular pathways.

Keywords: RUNX1T1; chemoresistance; colorectal cancer; gene expression.

MeSH terms

  • Apoptosis
  • Cell Proliferation / genetics
  • Cell Survival
  • Colorectal Neoplasms / genetics*
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Proto-Oncogene Proteins / genetics*
  • RNA, Messenger / metabolism
  • RUNX1 Translocation Partner 1 Protein
  • Transcription Factors / genetics*

Substances

  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RUNX1 Translocation Partner 1 Protein
  • RUNX1T1 protein, human
  • Transcription Factors