Deep sequencing identifies deregulation of microRNAs involved with vincristine drug-resistance of colon cancer cells

Int J Clin Exp Pathol. 2015 Sep 1;8(9):11524-30. eCollection 2015.

Abstract

Background: Vincristine (VCR) is a chemical that is widely used in tumor therapy. While long-term use can make tumor cells resistant to VCR, the underlying mechanisms of this resistance are still unclear.

Objective: This study aimed at investigating the role of microRNA (miRNA) in colon cancer drug resistance.

Methods: HCT-8 colon carcinoma cells were cultured and treated with different VCR concentrations to establish an HCT-8/VCR resistant cell line. Whole-genome screens, HiSeq 2500 sequencing, and bioinformatics methods were used to detect and analyze differences in miRNA expression between the drug-resistant HCT-8/VCR cells and non-resistant HCT-8 cells. Differential expression profiles of miRNAs were constructed based on sequencing result.

Results: The HCT-8/VCR resistant colon carcinoma cell line was established. With regard to the difference in drug resistance between HCT-8/VCR and HCT-8 cells, 24 miRNAs showed statistically significant differences in their expression (fold change > 4), of which 17 were up-regulated. Seven miRNAs were down-regulated.

Conclusion: As abnormal expression of miRNAs was associated with VCR resistance of colon carcinoma cells, differences in miRNA expression may play a key role in VCR resistance of colon cancer cells.

Keywords: Colon cancer; HCT-8; drug resistance; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / drug therapy*
  • Cell Line, Tumor
  • Colon / metabolism
  • Colonic Neoplasms / drug therapy*
  • Computational Biology
  • DNA, Complementary / genetics
  • Down-Regulation
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • MicroRNAs / genetics*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Up-Regulation
  • Vincristine / therapeutic use*

Substances

  • DNA, Complementary
  • MicroRNAs
  • Vincristine