ArticleOncogene2018
LRH1 enhances cell resistance to chemotherapy by transcriptionally activating MDC1 expression and attenuating DNA damage in human breast cancer.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- Balancing between cuproplasia and copper-dependent cell death: molecular basis and clinical implications of ATOX1 in cancer.Journal of experimental & clinical cancer research : CR · 2025Review
- DNA repair and the contribution to chemotherapy resistance.Genome medicine · 2025Review
- Role of Protein Regulators of Cholesterol Homeostasis in Immune Modulation and Cancer Pathophysiology.Endocrinology · 2025Review
- Decoding breast cancer treatment resistance through genetic, epigenetic, and immune-regulatory mechanisms: from molecular insights to translational perspectives.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Hepatocyte-specific NR5A2 deficiency induces pyroptosis and exacerbates non-alcoholic steatohepatitis by downregulating ALDH1B1 expression.Cell death & disease · 2024Article
- Review
- Chromatin-Associated SIN3B Protects Cancer Cells from Genotoxic Stress-Induced Apoptosis and Dictates DNA Damage Repair Pathway Choice.Molecular cancer research : MCR · 2023Article
- Label-Free Detection of T4 Polynucleotide Kinase Activity and Inhibition via Malachite Green Aptamer Generated from Ligation-Triggered Transcription.Biosensors · 2023Article
- MicroRNA-433-3p enhances chemosensitivity of glioma to cisplatin by downregulating NR5A2.Brain and behavior · 2022Article
- LINC00472 inhibits cell migration by enhancing intercellular adhesion and regulates H3K27ac level via interacting with P300 in renal clear cell carcinoma.Cell death discovery · 2022Article
- Differential Modulation of Nuclear Receptor LRH-1 through Targeting Buried and Surface Regions of the Binding Pocket.Journal of medicinal chemistry · 2022Article
- Liver Receptor homolog-1 Regulates Apoptosis of Bovine Ovarian Granulosa Cells by Progestogen Receptor Signaling Pathway.Animals : an open access journal from MDPI · 2022Article
- Article
- Macrophages and cancer stem cells: a malevolent alliance.Molecular medicine (Cambridge, Mass.) · 2021Review
- Prognostic significance and targeting tumor-associated macrophages in cancer: new insights and future perspectives.Breast cancer (Tokyo, Japan) · 2021Review
- Article
- LRH1 Acts as an Oncogenic Driver in Human Osteosarcoma and Pan-Cancer.Frontiers in cell and developmental biology · 2021Article
- Identification of Potential Genomic Alterations and the circRNA-miRNA-mRNA Regulatory Network in Primary and Recurrent Synovial Sarcomas.Frontiers in molecular biosciences · 2021Article
- Roles for MDC1 in cancer development and treatment.DNA repair · 2020Review
- Targeting Tumor-Associated Macrophages in Anti-Cancer Therapies: Convincing the Traitors to Do the Right Thing.Journal of clinical medicine · 2020Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver receptor homolog-1 (LRH1) has been shown to promote tumor proliferation and development. However, the functions of LRH1 in mediating cancer cells chemoresistance are still not clear. Here, we found LRH1 levels were significantly elevated in primary breast cancer tissues in patients who developed early recurrence. Similarly, adriamycin (ADR)-resistant breast cancer cell lines also exerted high LRH1 expression. Indeed, overexpression of LRH1 attenuated cytotoxicity of chemotherapeutic drugs ADR and cisplatin (DDP) in breast cancer cells in vitro and in nude mice tumor model. Comet and BrdU assays showed overexpression of LRH1 blocked breast cancer cells DNA damage by chemotherapeutic drug, whereas depletion of LRH1 enhanced DNA damage. Remarkably, knockdown of LRH1 decreased the levels and foci of DNA damage marker γH2AX induced by ADR and DDP. Furthermore, plasmid end-joining assay indicated that knockdown of LRH1 significantly decreased non-homologous end-joining (NHEJ)-mediated double-strand break (DSB) repair efficiencies. Afterwards, we provided evidences that LRH1 promoted MDC1 transcription by directly activating MDC1 promoter and therefore increased γH2AX levels. Importantly, a LRH1-binding site mapped between -1812 and -1804 bp of the proximal MDC1 promoter was identified. Moreover, LRH1 and MDC1 mRNA levels were positively correlated in recurrent breast cancer samples. These results implied LRH1 enhanced breast cancer cell chemoresistance by upregulating MDC1 and attenuating DNA damage. Additionally, we elucidated the coactivator NCOA3 acted synergistically with LRH1 to promote MDC1 expression and chemoresistance. Altogether, LRH1-MDC1 signaling might be considered as a novel molecular target for designing novel therapeutic regimen in chemotherapy resistance breast cancer.
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Registered trials
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