Investigating the therapeutic potential and mechanism of curcumin in breast cancer based on RNA sequencing and bioinformatics analysis

Breast Cancer. 2018 Mar;25(2):206-212. doi: 10.1007/s12282-017-0816-6. Epub 2017 Nov 14.

Abstract

Background: Breast cancer is a prevalent cancer in female. This study aims to investigate the therapeutic potential and mechanism of curcumin in breast cancer.

Methods: After cultivation, human breast cancer cells (MCF-7 cells) were treated with 0.1% (v/v) 15 µmol/ml curcumin-dimethylsulfoxide solution and 0.1% (v/v) dimethylsulfoxide, respectively, at 37 °C and 5% CO2 for 48 h. Total RNA was extracted, cDNA library was constructed, and cDNAs were amplified and sequenced. After data preprocessing, the Cufflinks software was utilized to identify differentially expressed genes (DEGs, |log2 fold change| > 0.5 and p value < 0.05). Then, functional and pathway enrichment analyses were performed through DAVID (p value < 0.05) and WebGestalt [false discovery rate (FDR) < 0.05], respectively. Furthermore, drug and disease association analyses (FDR < 0.05) were conducted through WebGestalt and DAVID, respectively. STRING was employed to construct protein-protein interaction (PPI) network (combined score > 0.4).

Results: After DEGs screening, 347 DEGs were identified. Up-regulated DEGs were enriched in 14 functions and 3 pathways, and associated with 12 drugs. Down-regulated DEGs were enriched in 14 functions and 9 pathways, and associated with 14 drugs. Moreover, 5 DEGs were associated with breast cancer, including PGAP3, MAP3K1, SERPINE1, PON2, and GSTO2. PPI network was constructed, and the top DEGs were FOS, VIM, FGF2, MAPK1, SPARC, TOMM7, PSMB10, TCEB2, SOCS1, COL4A1, UQCR11, SERPINE1, and ISG15.

Conclusion: Curcumin might have therapeutic potential in breast cancer through regulating breast cancer-related genes, including SERPINE1, PGAP3, MAP3K1, MAPK1, GSTO2, VIM, SPARC, and FGF2. However, validations are required.

Keywords: Breast cancer; Differentially expressed genes; Disease association analysis; Protein–protein interaction network; RNA sequencing.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Computational Biology / methods*
  • Curcumin / pharmacology*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Prognosis
  • Protein Interaction Maps
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Curcumin