ArticleFrontiers in genetics2022
Genome-wide analysis of the FOXA1 transcriptional regulatory network identifies super enhancer associated LncRNAs in tamoxifen resistance.
Article in Frontiers in genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- The Clinical Diagnostic Value of the Super-enhancer-associated Long Noncoding RNA RP11-803D5.4 and AC005592.2 in Colorectal Cancer.Current medicinal chemistry · 2026Article
- BRD4 PROTAC degrader enhances fulvestrant sensitivity in ER+ breast cancer via super-enhancer associated GREB1.Frontiers in oncology · 2026Article
- The role of super-enhancer-driven lncRNAs in cancer.Computational and structural biotechnology journal · 2025Review
- SE-lncRNAs in Cancer: Classification, Subcellular Localisation, Function and Corresponding TFs.Journal of cellular and molecular medicine · 2024Review
- Super enhancer lncRNAs: a novel hallmark in cancer.Cell communication and signaling : CCS · 2024Review
- Super-Enhancers and Their Parts: From Prediction Efforts to Pathognomonic Status.International journal of molecular sciences · 2024Review
- Development and validation of ferroptosis-related lncRNA signature and immune-related gene signature for predicting the prognosis of cutaneous melanoma patients.Apoptosis : an international journal on programmed cell death · 2023Article
- Epigenetic Alterations in DCIS Progression: What Can lncRNAs Teach Us?International journal of molecular sciences · 2023Review
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Authors and funding
3 authors at 1 institution in 1 country.
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Abstract
Breast cancer is the leading cause of death in female cancers, and what's worse, tamoxifen resistance occurs in almost 30% breast cancer patients and has seriously attenuated the therapeutic effect. It is widely studied that epigenetic regulation has played important role in the development of tamoxifen resistance. FOXA1 is a pioneer transcription factor that can translate epigenetic signature into transcription regulation and also drive genome-wide enhancer reprogramming in breast cancer. However, the chromatin super enhancer landscape orchestrated by FOXA1 and the key downstream targets of the FOXA1 oncogenic network in tamoxifen resistance remain elusive. Through analyzing the FOXA1 ChIP-seq data in tamoxifen sensitive MCF7 and tamoxifen resistant MCF7/TamR cells, we show that the FOXA1 chromatin occupancy is enhanced in both the promoter and enhancer regions, and the recruitment events may be E2 dependent in both MCF7 and MCF7/TamR cells. By integratively analyzing the FOXA1 ChIP-seq data and RNA-seq data of MCF7 and MCF7/TamR cells, we find that the enhanced or reduced FOXA1 chromatin binding densities may synchronize the transcriptional activity in tamoxifen resistance. Besides, we identify 1003 super enhancer associated protein coding genes and five super enhancer associated lncRNAs (ATP1A1-AS1, CASC11, CASC15, KCTD21-AS1, LINC00885) in tamoxifen resistance. By KM survival analysis, we find that high expression level of ATP1A1-AS1 and its sense transcript ATP1A1 indicates favorable clinical outcome among the luminal endocrine treated breast cancer patients. Further coexpression analysis indicates that ATP1A1-AS1 is significantly correlated with ATP1A1, and RT-qPCR results show that they both are downregulated in MCF7/TamR cells. Our study shows that the FOXA1 transcriptional regulatory network may promote the development of tamoxifen resistance, and identifies one super enhancer associated lncRNA ATP1A1-AS1 that may work as promising biomarker or drug target in tamoxifen resistance.
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