ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020
Olaparib and enzalutamide synergistically suppress HCC progression via the AR-mediated miR-146a-5p/BRCA1 signaling.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 36 citations in OpenAlex.
- PET imaging enables direct evaluation of ferroptosis in HCC synergistically induced by anti-PD-L1 and Olaparib.Experimental & molecular medicine · 2026Article
- TONSL Promotes Hepatocellular Carcinoma Progression by Inhibiting Apoptosis Through Homologous Recombination Repair.Cancer science · 2026Article
- Paradoxical oncogenic effects of hepatic Brca1 through modulating Bhmt.Scientific reports · 2026Article
- Nuclear ubiquitination permits Hippo-YAP signal for liver development and tumorigenesis.Nature chemical biology · 2025Article
- A pH/MMP-9 smart dual-responsive liposome GBE@LP co-delivers and controls the release of GB1107/BMS1166/Enzalutamide for liver cancer immunotherapy.Materials today. Bio · 2025Article
- Pharmacokinetic Interaction Between Olaparib and Regorafenib in an Animal Model.Pharmaceutics · 2024Article
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- Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study.International journal of molecular sciences · 2024Review
- Androgen receptor suppresses lung cancer invasion and increases cisplatin responseInternational journal of biological sciences · 2023Article
- Focus on the tumor microenvironment: A seedbed for neuroendocrine prostateFrontiers in cell and developmental biology · 2022Review
- Interaction between Non-Coding RNAs and Androgen Receptor with an Especial Focus on Prostate Cancer.Cells · 2021Review
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- Integrated analysis of the functions and prognostic values of RNA binding proteins in hepatocellular carcinoma.BMC gastroenterology · 2021Article
- Loss of exosomal miR-146a-5p from cancer-associated fibroblasts after androgen deprivation therapy contributes to prostate cancer metastasis.Journal of experimental & clinical cancer research : CR · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) is one of most common cancers worldwide, however, the treatment for advanced HCC remains unsatisfactory. We focused on the function of the androgen receptor (AR) in HCC and tried to find new treatment strategy based on antiandrogen enzalutamide (Enz). Here, we found that olaparib, a FDA-approved PARP inhibitor, could enhance the cytotoxicity in HCC cells with a lower BRCA1 expression, and suppressing the AR with either Enz or AR-shRNA could further increase the olaparib sensitivity to better suppress the HCC cell growth via a synergistic mechanism that may involve suppressing the expression of BRCA1 and other DNA damage response (DDR) genes. Mechanism studies revealed that Enz/AR signaling might transcriptionally regulate the miR-146a-5p expression via binding to the Androgen Response Elements on its 5' promoter region, which could then lead to suppress the homologous recombination-related BRCA1 expression via direct binding to the mRNA 3'UTR. Preclinical studies using an in vivo mouse model also demonstrated that combining Enz plus olaparib led to better suppression of the HCC progression. Together, these in vitro/in vivo data suggest that combining Enz and olaparib may help in the development of a novel therapy to better suppress the HCC progression.
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