ArticleBreast cancer research : BCR2019
The lncRNA MIR2052HG regulates ERα levels and aromatase inhibitor resistance through LMTK3 by recruiting EGR1.
Article in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 46 citations in OpenAlex.
- Interaction Between SNP Genotype and Efficacy of Anastrozole and Exemestane in Early-Stage Breast Cancer.Clinical pharmacology and therapeutics · 2021Trial
- Pharmacogenomics of aromatase inhibitors in postmenopausal breast cancer and additional mechanisms of anastrozole action.JCI insight · 2020Trial
- Progress of estrogen receptor and splice variants in ovarian carcinoma.Journal of ovarian research · 2026Review
- Long non-coding RNAs as modulators of endocrine therapy response in hormone receptor-positive breast cancer.Molecular biology reports · 2026Review
- Integrative analysis of lysosome-dependent cell death related molecular subtypes and prognosis prediction in papillary thyroid carcinoma.Journal of Cancer · 2026Article
- The role of UPR-related long noncoding RNAs in development of endocrine resistance in breast cancer.International journal of cancer · 2025Review
- Gain of Alternative Allele Expression of LINC02449 at rs149707223 in Schizophrenia and Bipolar Disorder: Inducing Synaptic Transmission and Behavioral Deficits in Mice.Nature communications · 2025Article
- Interactions between LncRNAs and MAPK signaling pathways in the pathogenesis of breast cancer.Cancer cell international · 2025Review
- LINC00626 drives tamoxifen resistance in breast cancer cells by interaction with UPF1.Scientific reports · 2025Article
- The lemur tail kinase family in neuronal function and disfunction in neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2024Review
- Targeting LINC00152 activates cAMP/CaCell death & disease · 2024Article
- Targeting LINC00152 activates cAMP/CabioRxiv : the preprint server for biology · 2023Article
- Landscape of NcRNAs involved in drug resistance of breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Preclinical-to-clinical Anti-cancer Drug Response Prediction and Biomarker Identification Using TINDL.Genomics, proteomics & bioinformatics · 2023Article
- Functional Relationships between Long Non-Coding RNAs and Estrogen Receptor Alpha: A New Frontier in Hormone-Responsive Breast Cancer Management.International journal of molecular sciences · 2023Review
- The Mechanisms of lncRNA-Mediated Multidrug Resistance and the Clinical Application Prospects of lncRNAs in Breast Cancer.Cancers · 2022Review
- Human Epididymis Protein 4 and Lewis y Enhance Chemotherapeutic Resistance in Epithelial Ovarian Cancer Through the p38 MAPK Pathway.Advances in therapy · 2022Article
- Role of estrogen receptors in health and disease.Frontiers in endocrinology · 2022Review
- Anastrozole Regulates Fatty Acid Synthase in Breast Cancer.Molecular cancer therapeutics · 2022Article
- Polymorphisms in lncRNAAging · 2021Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundOur previous genome-wide association study using the MA.27 aromatase inhibitors adjuvant trial identified SNPs in the long noncoding RNA MIR2052HG associated with breast cancer-free interval. MIR2052HG maintained ERα both by promoting AKT/FOXO3-mediated ESR1 transcription and by limiting ubiquitin-mediated ERα degradation. Our goal was to further elucidate MIR2052HG's mechanism of action.
methodsRNA-binding protein immunoprecipitation assays were performed to demonstrate that the transcription factor, early growth response protein 1 (EGR1), worked together with MIR2052HG to regulate that lemur tyrosine kinase-3 (LMTK3) transcription in MCF7/AC1 and CAMA-1 cells. The location of EGR1 on the LMTK3 gene locus was mapped using chromatin immunoprecipitation assays. The co-localization of MIR2052HG RNA and the LMTK3 gene locus was determined using RNA-DNA dual fluorescent in situ hybridization. Single-nucleotide polymorphisms (SNP) effects were evaluated using a panel of human lymphoblastoid cell lines.
resultsMIR2052HG depletion in breast cancer cells results in a decrease in LMTK3 expression and cell growth. Mechanistically, MIR2052HG interacts with EGR1 and facilitates its recruitment to the LMTK3 promoter. LMTK3 sustains ERα levels by reducing protein kinase C (PKC) activity, resulting in increased ESR1 transcription mediated through AKT/FOXO3 and reduced ERα degradation mediated by the PKC/MEK/ERK/RSK1 pathway. MIR2052HG regulated LMTK3 in a SNP- and aromatase inhibitor-dependent fashion: the variant SNP increased EGR1 binding to LMTK3 promoter in response to androstenedione, relative to wild-type genotype, a pattern that can be reversed by aromatase inhibitor treatment. Finally, LMTK3 overexpression abolished the effect of MIR2052HG on PKC activity and ERα levels.
conclusionsOur findings support a model in which the MIR2052HG regulates LMTK3 via EGR1, and LMTK3 regulates ERα stability via the PKC/MEK/ERK/RSK1 axis. These results reveal a direct role of MIR2052HG in LMTK3 regulation and raise the possibilities of targeting MIR2052HG or LMTK3 in ERα-positive breast cancer.
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