Role of β-Estradiol in MCF-7 Breast Cancer Cell Line Based on the Bioinformatics Analysis

Gynecol Obstet Invest. 2019;84(3):268-276. doi: 10.1159/000487945. Epub 2018 Nov 23.

Abstract

Background: This study aimed to investigate the action mechanism of β-estradiol in MCF-7 breast cancer (BC) cells.

Methods: The cell samples were sequenced using Hiseq 2000, including 2 MCF-7 controls and 2 samples treated with β-estradiol. Differentially expressed genes (DEGs) were screened using the NOISeq package in R, followed by the functions and pathways analyses using Database for Annotation, Visualization and Integrated Discovery. DEGs associated with β-estradiol were selected using the WbeGestalt software, and the corresponding target miRNAs of these genes were analyzed from different miRNA databases. Additionally, protein-protein interaction network of the drug-associated genes was constructed using Cytoscape.

Results: A total of 1,835 DEGs in BC samples were screened. Thereinto, DEGs associated with BC (17 upregulated and 28 downregulated DEGs) were involved in the regulation of cell proliferation, response to endogenous stimulus, and response to hormone stimulus, while the genes participated in several significant pathways. Cyclin D1, estrogen receptor 1, catechol-O-methyltransferase, and cathepsin D (CTSD; hub genes) were the predicted new genes associated with β-estradiol. Besides, hsa-miR-140-3p was the only target miRNA of CTSD.

Conclusion: β-Estradiol may play a key role in contributing to BC progression and metastasis by regulating the expression of the selected genes.

Keywords: Breast cancer; Differentially expressed genes; Protein-protein interaction network; β-Estradiol.

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Catechol O-Methyltransferase / genetics
  • Cathepsin D / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Computational Biology*
  • Disease Progression
  • Estradiol / pharmacology
  • Estradiol / physiology*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MCF-7 Cells
  • MicroRNAs / analysis
  • MicroRNAs / genetics
  • Protein Interaction Maps

Substances

  • MicroRNAs
  • Mirn140 microRNA, human
  • Estradiol
  • COMT protein, human
  • Catechol O-Methyltransferase
  • Cathepsin D