Alterations in expression profile of iron-related genes in colorectal cancer

Mol Biol Rep. 2013 Oct;40(10):5573-85. doi: 10.1007/s11033-013-2659-3.

Abstract

Iron can play a role in colorectal cancer (CRC) development. The expression of genes involved in iron metabolism and its regulation in CRC has not been investigated well. Also the correlation between the level of iron-related genes expression and cancer progression is not known. In this study we collected paired samples of primary adenocarcinoma and adjacent normal mucosa from 73 patients. We assessed the mRNA or miRNA levels of 21 genes and verify their association with clinicopathological characteristics of CRC patients. Our experiments revealed, that the level of divalent metal transporter 1 transcript is well correlated with mRNA levels of iron regulatory proteins (IRPs) in tumor specimens. We have shown, that IRP2 can also be engaged in the mRNA stabilization of other iron transporter-transferrin receptor 1 (TfR1) in early stage of disease, however, in more advanced stages of CRC, mRNA level of TfR1 is related to miR-31 level. For the first time we have shown, that ferroportin concentration is significantly associated with miR-194 level, causing the reduction of this transporter amount in tumor tissues of patients with more advanced stages of CRC. We have also shown the alterations in expressing profile of miR-31, miR-133a, miR-141, miR-145, miR-149, miR-182 and miR-194, which were observed even in the early stage of disease, and identified a set of genes, which take place in correct assigning of patients in dependence of CRC stage. These iron-related genes could become potential diagnostic or prognostic indicators for patients with CRC.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Discriminant Analysis
  • Disease Progression
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Genes, Neoplasm / genetics*
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Iron / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Mutation / genetics
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasm Staging
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Messenger
  • Iron