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Identification and Analysis of Estrogen Receptor α Promoting Tamoxifen Resistance-Related lncRNAs

Xiulei Zhang1, Shanjun Gao1, Zhen Li1

  • 1Department of Microbiome Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.

Biomed Research International
|May 19, 2020
PubMed

Insights

Researchers identified 49 long non-coding RNAs (lncRNAs) directly regulated by estrogen receptor alpha (ERα) that are linked to tamoxifen resistance in breast cancer. These ERα-regulated lncRNAs could serve as novel biomarkers for predicting treatment response and patient survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Estrogen receptor alpha (ERα)-positive breast cancer is common, with tamoxifen being a standard treatment.
  • Tamoxifen resistance occurs in 20-30% of patients, necessitating new therapeutic strategies and biomarkers.
  • Estrogen receptor alpha (ERα) signaling and long non-coding RNAs (lncRNAs) are implicated in tamoxifen resistance, but their direct regulatory relationship is unclear.

Purpose of the Study:

  • To identify long non-coding RNAs (lncRNAs) directly regulated by estrogen receptor alpha (ERα) in tamoxifen-resistant breast cancer.
  • To explore the potential of these ERα-regulated lncRNAs as diagnostic or prognostic markers for tamoxifen resistance.

Main Methods:

  • Reanalysis of publicly available ERα chromatin immunoprecipitation-sequencing (ChIP-seq) and RNA-sequencing (RNA-seq) data from tamoxifen-sensitive (MCF-7/WT) and tamoxifen-resistant (MCF-7/TamR) breast cancer cells.
  • Identification of differential ERα binding events and differentially expressed lncRNAs.
  • Overlap analysis to find ERα-bound and differentially expressed lncRNAs.

Main Results:

  • Differential ERα recruitment events were observed between sensitive and resistant cells, correlating with altered expression profiles.
  • 49 ERα-positively regulated lncRNAs were identified by overlapping ERα binding and differential expression data.
  • Specific lncRNAs (AC117383.1, AC144450.1, RP11-15H20.6, ATXN1-AS1) showed negative correlation with patient survival, while others (ELOVL2-AS1, PCOLCE-AS1, ITGA9-AS1, FLNB-AS1) showed positive correlation.

Conclusions:

  • Estrogen receptor alpha (ERα) directly regulates specific long non-coding RNAs (lncRNAs) involved in tamoxifen resistance.
  • These identified lncRNAs represent potential novel biomarkers for diagnosing and predicting prognosis in tamoxifen-resistant breast cancer.

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