Analysis of miRNA-mRNA network reveals miR-140-5p as a suppressor of breast cancer glycolysis via targeting GLUT1

Epigenomics. 2019 Jul;11(9):1021-1036. doi: 10.2217/epi-2019-0072. Epub 2019 Jun 11.

Abstract

Aim: Aerobic glycolysis is characteristic of breast cancer. Comprehensive expression profiles of key proteins, their prognosis and detailed relationships between miRNAs and mRNAs remain unclear. Materials & methods: Oncomine database, Kaplan-Meier overall survival and miRNA-mRNA network analysis were performed. A key miRNA was identified and explored in vitro and in vivo. Results & conclusion: Eleven key glycolytic proteins were found with higher expression and poor prognosis: GLUT1, SLC2A5, HK1, PFKP, ALDOA, TPI1, GAPDH, PGK1, ENO1, GOT1 and GOT2. Seven miRNAs were predicted targeting 11 key glycolytic proteins: miR-140-5p, miR-3064-5p, miR-152-3p, miR-449b-5p, miR-449a, miR-194-5p and miR-34a-5p. Among them, miR-140-5p was found to be downregulated in breast cancer and directly targeted GLUT1, resulting in an antiglycolytic and antiproliferative effect.

Keywords: GLUT1; SLC2A1; breast cancer; breast carcinoma; expression; glycolysis; miR-140-5p; miRNA–mRNA network; prognosis; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Glucose Transporter Type 1 / genetics*
  • Glycolysis / genetics*
  • Humans
  • MicroRNAs / genetics*
  • Prognosis
  • RNA, Messenger / genetics

Substances

  • Biomarkers, Tumor
  • Glucose Transporter Type 1
  • MicroRNAs
  • Mirn140 microRNA, human
  • RNA, Messenger
  • SLC2A1 protein, human