LncRNA LINP1 confers tamoxifen resistance and negatively regulated by ER signaling in breast cancer

Cell Signal. 2020 Apr;68:109536. doi: 10.1016/j.cellsig.2020.109536. Epub 2020 Jan 10.


Tamoxifen (TAM) is frequently used to treat patients with estrogen receptor-positive (ER+) breast cancer; however, the development of endocrine resistance represents a major impediment for successful treatment. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) may serve critical roles in regulating endocrine resistance in breast cancer. In the present study, it was determined that the expression of lncRNA in nonhomologous end joining pathway 1 (LINP1) was increased in tamoxifen-resistant breast cancer cells, and that LINP1 knockdown significantly attenuated the tamoxifen resistance and viability of tamoxifen-resistant breast cancer cells in vitro and in vivo. LINP1 knockdown increased apoptosis in cells following treatment with tamoxifen. Furthermore, LINP1 overexpression resulted in increased cell mobility by regulating the EMT process. Mechanistically, LINP1 is a direct target of ER-mediated transcriptional repression, and both tamoxifen treatment and hormone deprivation increased the expression of LINP1. LINP1 overexpression was associated with downregulation of the levels of ER protein and attenuated the estrogen response, which is a pivotal contributing factor to anti-estrogen resistance. Taken together, the present study highlights the pivotal role of LINP1 in tamoxifen resistance, which may serve as a potential target to improve the effectiveness and efficacy of tamoxifen treatment in breast cancer.

Keywords: Apoptosis; Breast cancer; Estrogen signaling; Long non-coding RNA LINP1; Tamoxifen resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Estrogens / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Gene Knockdown Techniques
  • Humans
  • Mice, Nude
  • Neoplasm Invasiveness
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction* / drug effects
  • Signal Transduction* / genetics
  • Tamoxifen / pharmacology
  • Tamoxifen / therapeutic use*
  • Transcription, Genetic / drug effects
  • Up-Regulation / drug effects
  • Up-Regulation / genetics


  • Estrogens
  • LINP1 non-coding RNA, human
  • RNA, Long Noncoding
  • Tamoxifen