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Comprehensive Transcriptomic Analysis Reveals Dysregulated Competing Endogenous RNA Network in Endocrine Resistant

Liang Gao1, Kunwei Shen2, Ni Yin3

  • 1Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.

Frontiers in Oncology
|December 16, 2020
PubMed
Abstract

Insights

This study profiles non-coding RNAs (ncRNAs) in endocrine-resistant breast cancer cells, revealing their role in tamoxifen and fulvestrant resistance. Findings offer new biomarkers and therapeutic targets for overcoming resistance.

Area of Science:

  • Genomics
  • Molecular Biology
  • Oncology

Background:

  • Hormone receptor-positive breast cancer treatment relies on tamoxifen and fulvestrant.
  • Acquired resistance to endocrine therapy limits treatment efficacy.
  • Non-coding RNAs (ncRNAs) are implicated in endocrine resistance, but their specific roles are unclear.

Purpose of the Study:

  • To comprehensively profile ncRNAs in tamoxifen- and fulvestrant-resistant breast cancer cells.
  • To investigate the role of ncRNAs in acquired endocrine resistance.
  • To identify potential biomarkers and therapeutic targets for overcoming endocrine resistance.

Main Methods:

  • Microarray analysis of endocrine-sensitive and resistant breast cancer cell lines (MCF-7, LCC2, LCC9).
  • Gene ontology and pathway analysis for functional prediction of differentially expressed ncRNAs.
  • Construction of competing endogenous RNA (ceRNA) regulatory networks (lncRNA-mRNA, circRNA-mRNA, microRNA-mRNA, and integrated networks).

Main Results:

  • Identified significant differential expression of 3,129 long non-coding RNAs (lncRNAs), 13,556 circular RNAs (circRNAs), 132 microRNAs, and 3,358 messenger RNAs (mRNAs).
  • Constructed co-expression and regulatory networks (lncRNA-microRNA-mRNA, circRNA-microRNA-mRNA) to illustrate ncRNA crosstalk and transcriptomic regulation.
  • Detailed ncRNA profiles in endocrine-resistant cells were established.

Conclusions:

  • Provides a comprehensive ncRNA profile in tamoxifen- and fulvestrant-resistant breast cancer.
  • Enhances understanding of the mechanisms underlying endocrine resistance.
  • Highlights potential novel biomarkers and therapeutic strategies to combat endocrine resistance in breast cancer.
Keywords:
breast cancerendocrine resistancefulvestrantnon-coding RNAtamoxifentranscriptome profile

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