Role of class I histone deacetylases in the regulation of maspin expression in prostate cancer
| Autor: | Mario Candamo, Sanjeev Shukla, Sanjay Gupta, Shiv Verma, Rajnee Kanwal, Eswar Shankar, Mitali Pandey, Ata Abbas, Gregory T. MacLennan |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cancer Research Apoptosis Biology Hydroxamic Acids Histone Deacetylases Article Epigenesis Genetic Histones 03 medical and health sciences Histone H3 chemistry.chemical_compound Prostate cancer 0302 clinical medicine DU145 LNCaP Biomarkers Tumor Tumor Cells Cultured medicine Humans Promoter Regions Genetic Molecular Biology Serpins Cell Proliferation Maspin Prostatic Neoplasms Cancer Sodium butyrate DNA Methylation Prognosis medicine.disease Gene Expression Regulation Neoplastic Histone Deacetylase Inhibitors 030104 developmental biology Trichostatin A chemistry 030220 oncology & carcinogenesis Cancer research medicine.drug |
| Zdroj: | Mol Carcinog |
| ISSN: | 1098-2744 0899-1987 |
| Popis: | Maspin repression is frequently observed in prostate cancer; however, the molecular mechanism(s) causing the loss is not completely understood. Here, we demonstrate that inhibition of class I histone deacetylases (HDACs) mediates re-expression of maspin which plays an essential role in suppressing proliferation and migration capability in prostate cancer cells. Human prostate cancer LNCaP and DU145 cells treated with HDAC inhibitors, sodium butyrate, and trichostatin A, resulted in maspin re-expression. Interestingly, an exploration into the molecular mechanisms demonstrates that maspin repression in prostate tumor and human prostate cancer cell lines occurs via epigenetic silencing through an increase in HDAC activity/expression, independent of promoter DNA hypermethylation. Furthermore, transcriptional activation of maspin was accompanied with the suppression of HDAC1 and HDAC8 with significant p53 enrichment at the maspin promoter associated with an increase in histone H3/H4 acetylation. Our results provide evidence of maspin induction as a critical epigenetic event altered by class I HDACs in the restoration of balance to delay proliferation and migration ability of prostate cancer cells. |
| Databáze: | OpenAIRE |
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