The miR-34a-LDHA axis regulates glucose metabolism and tumor growth in breast cancer

Sci Rep. 2016 Feb 23:6:21735. doi: 10.1038/srep21735.

Abstract

Lactate dehydrogenase A (LDHA) is involved in a variety of cancers. The purpose of this study was to investigate the expression, prognostic roles and function of LDHA in breast cancer. We found that LDHA was upregulated in both breast cancer cell lines and clinical specimens using quantitative real-time PCR (qRT-PCR). Immunohistochemistry (IHC) analysis of tissue microarrays (TMAs) showed that high LDHA expression was associated with cell proliferation, metastasis and poor patient overall survival (OS) and disease free survival (DFS). Furthermore, we found that LDHA promoted glycolysis and cell proliferation in vitro and in vivo. We also performed luciferase reporter assays and found that LDHA was a direct target of miR-34a. Repression of LDHA by miR-34a suppressed glycolysis and cell proliferation in breast cancer cells in vitro. Our findings provide clues regarding the role of miR-34a as a tumor suppressor in breast cancer through the inhibition of LDHA both in vitro and in vivo. Targeting LDHA through miR-34a could be a potential therapeutic strategy in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Glucose / metabolism*
  • Glycolysis / genetics*
  • Humans
  • Injections, Subcutaneous
  • Lactate Dehydrogenases / antagonists & inhibitors
  • Lactate Dehydrogenases / genetics*
  • Lactate Dehydrogenases / metabolism
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Transplantation
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Sequence Alignment
  • Signal Transduction
  • Survival Analysis

Substances

  • MIRN34 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • Lactate Dehydrogenases
  • D-lactate dehydrogenase
  • Luciferases
  • Glucose