[Overexpression of microRNAs miR-9, -98, and -199 Correlates with the Downregulation of HK2 Expression in Colorectal Cancer]

Mol Biol (Mosk). 2018 Mar-Apr;52(2):220-230. doi: 10.7868/S0026898418020052.
[Article in Russian]

Abstract

Glycolysis activation is one of the main features of energy metabolism in cancer cells that is associated with the increase in glycolytic enzyme synthesis, primarily, hexokinases (HKs), in many types of tumors. Conversely, in colorectal cancer (CRC) the decrease in the expression of HK2 gene, which encodes one of the key rate-limiting enzyme of glycolysis, was revealed, thus, the study of the mechanisms of its inhibition in CRC is of particular interest. To search for potential microRNAs, inhibiting the expression of HK2 in CRC, we have performed the analysis of data from "The Cancer Genome Atlas" (TCGA) and five microRNA-mRNA target interaction databases (TargetScan, DIANA microT, mirSVR (miRanda), PicTar, and miRTarBase) using original CrossHub software. Seven microRNAs containing binding site on mRNA HK2, which expression is negatively correlated with HK2 expression, were selected for further analysis. The expression levels of these microRNAs and mRNA HK2 were estimated by quantitative PCR on a set of CRC samples. It has been shown, that the expression of three microRNAs (miR-9-5p, -98-5p, and -199-5p) was increased and correlated negatively with mRNA level of HK2 gene. Thus, downregulation of HK2 gene may be caused by its negative regulation through microRNAs miR-9-5p, -98-5p, and -199-5p.

Keywords: HK2; colorectal cancer; glycolysis; microRNA; qPCR.

MeSH terms

  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Down-Regulation*
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Hexokinase / biosynthesis*
  • Hexokinase / genetics
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*

Substances

  • MIRN92 microRNA, human
  • MIRN98 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • mirn199 microRNA, human
  • HK2 protein, human
  • Hexokinase