Circulating miR-182 is a biomarker of colorectal adenocarcinoma progression

Oncotarget. 2014 Aug 30;5(16):6611-9. doi: 10.18632/oncotarget.2245.

Abstract

MiR-182 expression was evaluated by qRT-PCR and in situ hybridization in 20 tubular adenomas, 50 colorectal carcinoma (CRC), and 40 CRC liver metastases. Control samples obtained from patients with irritable bowel syndrome, or tumor-matched normal colon mucosa were analyzed (n=50). MiR-182 expression increased progressively and significantly along with the colorectal carcinogenesis cascade, and in CRC liver metastases. The inverse relation between miR-182 and the expression of its target gene ENTPD5 was investigated by immunohistochemical analysis. We observed that normal colocytes featured a strong ENTPD5 cytoplasmic expression whereas a significantly and progressively lower expression was present along with dedifferentiation of the histologic phenotype. Plasma samples from 51 CRC patients and controls were tested for miR-182 expression. Plasma miR-182 concentrations were significantly higher in CRC patients than in healthy controls or patients with colon polyps at endoscopy. Moreover, miR-182 plasma levels were significantly reduced in post-operative samples after radical hepatic metastasectomy compared to preoperative samples. Our results strengthen the hypothesis of a central role of miR-182 dysregulation in colon mucosa transformation, demonstrate the concomitant progressive down-regulation of ENTPD5 levels during colon carcinogenesis, and indicate the potential of circulating miR-182 as blood based biomarker for screening and monitoring CRC during the follow-up.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Aged
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Female
  • HEK293 Cells
  • Humans
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Oncogene Proteins / genetics
  • Pyrophosphatases / genetics
  • Transfection
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • Mirn182 microRNA, human
  • Oncogene Proteins
  • ENTPD5 protein, human
  • Pyrophosphatases