lncRNA CYTOR promotes tamoxifen resistance in breast cancer cells via sponging miR‑125a‑5p

Int J Mol Med. 2020 Feb;45(2):497-509. doi: 10.3892/ijmm.2019.4428. Epub 2019 Dec 16.

Abstract

Development of resistance to endocrine therapy, such as tamoxifen, remains a tricky clinical problem during the treatment of breast cancer. Accumulating evidence suggested that dysregulation of long noncoding (lnc_RNAs contributes to the development of tamoxifen resistance. In the current study, via screening, cytoskeleton regulator RNA (CYTOR) was identified as the most significantly elevated lncRNA in the established tamoxifen resistant MCF7 cell lines (MCF7/TAM1 and MCF7/TAM2) compared with the parental MCF7 cells (MCF7‑P). The CCK‑8 assay indicated that silencing of CYTOR increased the sensitivity of MCF7/TAM1 and MCF7/TAM2 to tamoxifen treatment. Using bioinformatic analysis, it was predicted that microRNA (miR)‑125a‑5p might bind to CYTOR and the expression of miR‑125a‑5p was negatively correlated with CYTOR in the tumor tissues of breast cancer. In addition, RT‑qPCR and dual luciferase assays validated that CYTOR directly repressed miR‑125a‑5p expression in breast cancer cells. Through regulation of miR‑125a‑5p, CYTOR elevated serum response factor (SRF) expression and activated Hippo and mitogen associated protein kinase signaling pathways to promote breast cancer cell survival upon tamoxifen treatment. In the collected tumor tissues of breast cancer in the present study, high expression of CYTOR was detected in tissues from patients with no response to tamoxifen compared with those from patients who were not treated with tamoxifen. A positive correlation between CYTOR and SRF mRNA expression was observed in tissues collected from patients with breast cancer. In conclusion, the results of the present study demonstrated a pivotal role of CYTOR in mediating tamoxifen resistance in breast cancer.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA, Long Noncoding / genetics*
  • Tamoxifen / pharmacology*
  • Tamoxifen / therapeutic use

Substances

  • Antineoplastic Agents, Hormonal
  • MIRN125 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Tamoxifen