MiR-361-5p inhibits glycolytic metabolism, proliferation and invasion of breast cancer by targeting FGFR1 and MMP-1

J Exp Clin Cancer Res. 2017 Nov 13;36(1):158. doi: 10.1186/s13046-017-0630-1.


Background: MicroRNAs function as key regulators in various human cancers, including breast cancer (BC). MiR-361-5p has been proved to be a tumor suppressor in colorectal cancer and gastric cancer in our previous study. In this study, we aim to find out the function of miR-361-5p in breast cancer progression and elaborate the mechanism that miR-361-5p acts its function in breast cancer.

Methods and results: Here we reported that miR-361-5p was down-regulated in breast cancer tissue compared with normal breast tissue and the expression of miR-361-5p was positively associated with prognosis in BC patients. Functional studies showed that overexpression of miR-361-5p suppressed the proliferation, invasion and metastasis of breast cancer cells both in vivo and in vitro. Mechanistically, we found that miR-361-5p inhibited the proliferation of BC cells by suppressing glycolysis. FGFR1, a promoter of glycolysis-related enzyme, was identified as the target of miR-361-5p that promoted glycolysis and repressed oxidative phosphorylation. Furthermore, we demonstrated that miR-361-5p inhibited breast cancer cells invasion and metastasis by targeting MMP-1. An inverse expression pattern was also found between miR-361-5p and FGFR1 or MMP-1 in a cohort of 60 BC tissues.

Conclusion: Our results indicate that miR-361-5p inhibits breast cancer cells glycolysis and invasion by respectively repressing FGFR1 and MMP-1, suggesting that miR-361-5p and its targets may serve as therapeutic targets in breast cancer treatment.

Keywords: FGFR1; Glycolysis; MMP-1; miR-361-5p.

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycolysis*
  • Humans
  • Isoenzymes / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Lactate Dehydrogenase 5
  • MCF-7 Cells
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 1 / metabolism
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Oxidative Phosphorylation
  • Prognosis
  • Protein Serine-Threonine Kinases / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics*
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism


  • Isoenzymes
  • MIRN361 microRNA, human
  • MicroRNAs
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • L-Lactate Dehydrogenase
  • Lactate Dehydrogenase 5
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1
  • Protein Serine-Threonine Kinases
  • MMP1 protein, human
  • Matrix Metalloproteinase 1