2022 Fiscal Year Final Research Report
Functional analysis of prostate cancer bone metastasis-related lncRNA and establishment of the basis for the development of new therapies
| Project/Area Number |
18K09181
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | International University of Health and Welfare (2021-2022)
Keio University (2020)
Nippon Medical School (2018-2019) |
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Principal Investigator |
Misawa Aya 国際医療福祉大学, 医学部, 講師 (20598453)
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| Co-Investigator(Kenkyū-buntansha) |
瀧澤 俊広 日本医科大学, 大学院医学研究科, 大学院教授 (90271220)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Keywords | lncRNA / 前立腺がん / 骨転移 / サイトカイン / インテグリン |
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| Outline of Final Research Achievements |
In this study, we found that homeobox A11 antisense RNA (HOXA11-AS), a highly expressed lncRNA in cell lines derived from prostate cancer bone metastases, promotes cell invasion and proliferation of PC3 prostate cancer cells. Transcription factor homeobox B13 (HOXB13) was identified as an upstream regulator of HOXA11-AS. HOXA11-AS regulated bone metastasis-associated C-C motif chemokine ligand 2 (CCL2)/C-C chemokine receptor type 2 (CCR2) signaling in both PC3 prostate cancer cells and SaOS2 osteoblastic cells. The HOXB13/HOXA11-AS axis also regulated integrin subunits specific to prostate cancer bone metastasis. Furthermore, conditioned medium containing HOXA11-AS secreted from PC3 cells could induce the expression of CCL2 and IBSP in SaOS2 osteoblastic cells. These results suggest that prostate cancer HOXA11-AS and HOXB13 promote metastasis by regulation of CCL2/CCR2 and integrin signals in autocrine and paracrine manners.
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| Free Research Field |
腫瘍免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
lncRNA は多様な臓器のがんで異常発現することが知られている。HOXA11-AS はがんバイオマーカーとして同定されている免疫関連 lncRNAである。本研究より、HOXA11-ASが前立腺がんの骨転移に主要な役割を果たしていることが示唆された。また、lncRNA が免疫チェックポイント阻害剤との奏効と相関する結果も得られており、HOXA11-ASと発がんとの関係の解明は抗がん剤治療や免疫療法を組み合わせた新たな複合療法の開発につながることが期待できる。
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