SNP rs9364554 Modulates Androgen Receptor Binding and Drug Response in Prostate Cancer
(1) Background: Prostate cancer treatment efficacy is significantly influenced by androgen receptor (AR) signaling pathways. SLC22A3, a membrane transporter, has been linked to SNP rs9364554 risk loci for drug efficacy in prostate cancer. (2) Methods: We examined the location of SNP rs9364554 in the...
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2025-01-01
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| author | Yuqian Yan Lei Shi Tao Ma Liguo Wang Haojie Huang |
| author_facet | Yuqian Yan Lei Shi Tao Ma Liguo Wang Haojie Huang |
| author_sort | Yuqian Yan |
| collection | DOAJ |
| description | (1) Background: Prostate cancer treatment efficacy is significantly influenced by androgen receptor (AR) signaling pathways. SLC22A3, a membrane transporter, has been linked to SNP rs9364554 risk loci for drug efficacy in prostate cancer. (2) Methods: We examined the location of SNP rs9364554 in the genome and utilized TCGA and other publicly available datasets to analyze the association of this SNP with <i>SLC22A3</i> transcription levels. We verified onco-mining findings in prostate cancer cell lines using quantitative PCR and Western blots. Additionally, we employed electrophoretic mobility shift assay (EMSA) to detect the binding affinity of transcription factors to this SNP. The ChIP-Seq was used to analyze the enrichment of H3K27ac on the <i>SLC22A3</i> promoter. (3) Results: In this study, we revealed that SNP rs9364554 resides in the <i>SLC22A3</i> gene and affects its transcription. The downregulation of SLC22A3 is associated with drug resistance. More importantly, we found that this SNP has different binding affinities with transcription factors, specifically FOXA1 and AR, which significantly affects their regulation of <i>SLC22A3</i> transcription. (4) Conclusions: Our findings highlight the potential of using this SNP as a biomarker for predicting chemotherapeutic outcomes and uncover possible mechanisms underlying drug resistance in advanced prostate cancers. More importantly, it provides a clinical foundation for targeting FOXA1 to enhance drug efficacy in prostate cancer patients. |
| format | Article |
| id | doaj-art-f59f29c5cc044b2dadfa3677b04dc47a |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-f59f29c5cc044b2dadfa3677b04dc47a2025-01-24T13:25:02ZengMDPI AGBiomolecules2218-273X2025-01-011516410.3390/biom15010064SNP rs9364554 Modulates Androgen Receptor Binding and Drug Response in Prostate CancerYuqian Yan0Lei Shi1Tao Ma2Liguo Wang3Haojie Huang4Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USADepartment of Radiation Oncology, Cancer Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou 310025, ChinaDivision of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USADivision of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USADepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA(1) Background: Prostate cancer treatment efficacy is significantly influenced by androgen receptor (AR) signaling pathways. SLC22A3, a membrane transporter, has been linked to SNP rs9364554 risk loci for drug efficacy in prostate cancer. (2) Methods: We examined the location of SNP rs9364554 in the genome and utilized TCGA and other publicly available datasets to analyze the association of this SNP with <i>SLC22A3</i> transcription levels. We verified onco-mining findings in prostate cancer cell lines using quantitative PCR and Western blots. Additionally, we employed electrophoretic mobility shift assay (EMSA) to detect the binding affinity of transcription factors to this SNP. The ChIP-Seq was used to analyze the enrichment of H3K27ac on the <i>SLC22A3</i> promoter. (3) Results: In this study, we revealed that SNP rs9364554 resides in the <i>SLC22A3</i> gene and affects its transcription. The downregulation of SLC22A3 is associated with drug resistance. More importantly, we found that this SNP has different binding affinities with transcription factors, specifically FOXA1 and AR, which significantly affects their regulation of <i>SLC22A3</i> transcription. (4) Conclusions: Our findings highlight the potential of using this SNP as a biomarker for predicting chemotherapeutic outcomes and uncover possible mechanisms underlying drug resistance in advanced prostate cancers. More importantly, it provides a clinical foundation for targeting FOXA1 to enhance drug efficacy in prostate cancer patients.https://www.mdpi.com/2218-273X/15/1/64SNP rs9364554SLC22A3ARFOXA1drug efficacyprostate cancer |
| spellingShingle | Yuqian Yan Lei Shi Tao Ma Liguo Wang Haojie Huang SNP rs9364554 Modulates Androgen Receptor Binding and Drug Response in Prostate Cancer Biomolecules SNP rs9364554 SLC22A3 AR FOXA1 drug efficacy prostate cancer |
| title | SNP rs9364554 Modulates Androgen Receptor Binding and Drug Response in Prostate Cancer |
| title_full | SNP rs9364554 Modulates Androgen Receptor Binding and Drug Response in Prostate Cancer |
| title_fullStr | SNP rs9364554 Modulates Androgen Receptor Binding and Drug Response in Prostate Cancer |
| title_full_unstemmed | SNP rs9364554 Modulates Androgen Receptor Binding and Drug Response in Prostate Cancer |
| title_short | SNP rs9364554 Modulates Androgen Receptor Binding and Drug Response in Prostate Cancer |
| title_sort | snp rs9364554 modulates androgen receptor binding and drug response in prostate cancer |
| topic | SNP rs9364554 SLC22A3 AR FOXA1 drug efficacy prostate cancer |
| url | https://www.mdpi.com/2218-273X/15/1/64 |
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