MicroRNA-335-5p and -3p synergize to inhibit estrogen receptor alpha expression and promote tamoxifen resistance

FEBS Lett. 2017 Jan;591(2):382-392. doi: 10.1002/1873-3468.12538. Epub 2017 Jan 12.

Abstract

microRNAs (miRNAs) are small noncoding RNA molecules involved in the regulation of gene expression and play critical roles in human malignancies. Next-generation sequencing analysis of the MCF-7 breast cancer cell line overexpressing miR-335-5p and miR-335-3p demonstrated that the miRNA duplex repressed genes involved in the ERα signaling pathway, and enhanced resistance of MCF-7 cells to the growth inhibitory effects of tamoxifen. These data suggest that despite its conventional role in tumor suppression, the miR-335 transcript can also play an oncogenic role in promoting agonistic estrogen signaling in a cancerous setting.

Keywords: breast cancer; endocrine resistance; estrogen receptor; isoform; miRNA-335; microRNA.

Publication types

  • Letter

MeSH terms

  • Breast Neoplasms / genetics
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor alpha / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • MAP Kinase Signaling System / drug effects
  • MCF-7 Cells
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tamoxifen / pharmacology*

Substances

  • ESR1 protein, human
  • Estrogen Receptor alpha
  • MIRN335 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Tamoxifen