Integrated network analysis identifies hsa-miR-4756-3p as a regulator of FOXM1 in Triple Negative Breast Cancer

Sci Rep. 2019 Sep 25;9(1):13830. doi: 10.1038/s41598-019-50248-3.

Abstract

Both aberrantly expressed mRNAs and micro(mi)RNAs play important roles in cancer cell function, which makes integration analysis difficult. In this study, we first applied master regulator analysisalgorithm and confirmed hsa-miR-4756-3p as a candidate miRNA in triple negative breast cancer (TNBC) patients; hsa-miR-4756-3p could regulate TNBC cell line apoptosis, proliferation, migration, and cell cycle as well as suppress TGF-β1 signalling andtumour growth. In TNBC, forkhead box protein M1 (FOXM1)was found to be an hsa-miR-4756-3p target gene, and FOXM1 knockout completely inhibited hsa-miR-4756-3p-induced cell migration and metastasis, TGF-β1 signalling, and epithelial mesenchymal signal activation, which indicated that hsa-miR-4756-3p functions via the FOXM1-TGFβ1-EMT axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Animals
  • Apoptosis
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Computational Biology / methods*
  • Epithelial-Mesenchymal Transition
  • Female
  • Forkhead Box Protein M1 / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Transplantation
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology*

Substances

  • 3' Untranslated Regions
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • MicroRNAs