Elucidation of epigenome-mediated mechanism for growth supression in castration-resistant prostate cancer
| Project/Area Number |
15K21282
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Human pathology
Tumor biology
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| Research Institution | Nagoya City University |
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Principal Investigator |
SATO Shinya 名古屋市立大学, 大学院医学研究科, 研究員 (30464564)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | HDAC阻害剤 / エピゲノム機構 / microRNA / アンドロゲン受容体 / ホルモン治療抵抗性前立腺癌 / heterogeneity / 網羅的増殖抑制メカニズム / 癌治療 / miRNA / エピゲノム制御 / 予後 / histone acetylation / prostate cancer / androgen receptor / HDAC inhibitor / hormone therapy |
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| Outline of Final Research Achievements |
Targeting androgen receptor (AR) is one of the effective approaches for treatment of prostate cancers. Histone deacetylase (HDAC) alters the epigenetic status of tumor-associated genes, including those for miRNAs, and affects the behavior of cancers. We examined the molecular effects of a HDAC inhibitor, OBP-801, on prostate cancers. Treatment with OBP-801 efficiently suppressed cell growth of prostate cancer lines, together with AR downregulation, regardless of their hormone sensitivity. Among the upregulated miRNAs after OBP-801 treatment in the cell lines, miR-320a, was the most closely associated with AR expression. An miR-320a mimic suppressed AR protein expression together with growth suppression. Our data demonstrated that OBP-801 effectively suppressed AR activity via upregulation of miR-320a, which resulted in tumor cell growth suppression of prostate cancers. OBP-801 may be a promising AR-targeting reagent in AR-positive prostate cancer regardless of androgen dependency.
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Report
(3 results)
Research Products
(6 results)
