Radiation and SN38 treatments modulate the expression of microRNAs, cytokines and chemokines in colon cancer cells in a p53-directed manner

Oncotarget. 2015 Dec 29;6(42):44758-80. doi: 10.18632/oncotarget.5815.

Abstract

Aberrant expression of miRNAs, cytokines and chemokines are involved in pathogenesis of colon cancer. However, the expression of p53 mediated miRNAs, cyto- and chemokines after radiation and SN38 treatment in colon cancer remains elusive. Here, human colon cancer cells, HCT116 with wild-type, heterozygous and a functionally null p53, were treated by radiation and SN38. The expression of 384 miRNAs was determined by using the TaqMan® miRNA array, and the expression of cyto- and chemokines was analyzed by Meso-Scale-Discovery instrument. Up- or down-regulations of miRNAs after radiation and SN38 treatments were largely dependent on p53 status of the cells. Cytokines, IL-6, TNF-α, IL-1β, Il-4, IL-10, VEGF, and chemokines, IL-8, MIP-1α were increased, and IFN-γ expression was decreased after radiation, whereas, IL-6, IFN-γ, TNF-α, IL-1β, Il-4, IL-10, IL-8 were decreased, and VEGF and MIP-1α were increased after SN38 treatment. Bioinformatic analysis pointed out that the highly up-regulated miRNAs, let-7f-5p, miR-455-3p, miR-98, miR-155-5p and the down-regulated miRNAs, miR-1, miR-127-5p, miR-142-5p, miR-202-5p were associated with colon cancer pathways and correlated with cyto- or chemokine expression. These miRNAs have the potential for use in colon cancer therapy as they are related to p53, pro- or anti-inflammatory cyto- or chemokines after the radiation and SN38 treatment.

Keywords: chemokines; colon cancer cells; cytokines; miRNAs; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacology
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Chemoradiotherapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Computational Biology
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Databases, Genetic
  • Dose-Response Relationship, Drug
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Heterozygote
  • Humans
  • Inhibitory Concentration 50
  • Irinotecan
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mutation
  • Radiation Dosage
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • Chemokines
  • Cytokines
  • MicroRNAs
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Irinotecan
  • Camptothecin