| Project/Area Number |
20K06439
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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 42020:Veterinary medical science-related
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| Research Institution | Nippon Veterinary and Life Science University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 犬 / 前立腺癌 / microRNA / micro RNA |
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| Outline of Research at the Start |
犬前立腺癌の多くが悪性腫瘍であり、早期に遠隔転移や局所浸潤が認められるが、有効性が高い治療法は存在しない。Micro RNA（miRNA）は、標的遺伝子の発現調節によって腫瘍の増殖・分化、遊走、転移に関わること、また、様々な腫瘍においてmiRNAの発現異常がみられるため、有望な治療標的と考えらるが、犬前立腺癌におけるmiRNA発現異常に関わる分子機構の詳細は不明である。本研究の目的では、犬前立腺癌細胞株を用いて、前立腺癌組織中で発現変化が認められるmiRNAを標的として、人為的にmiRNAの発現制御を行い、腫瘍性増殖機構および転移・浸潤機構に関わる分子を同定し、病態形成機構を明らかにする。
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| Outline of Final Research Achievements |
In this study, three canine prostate cancer cell lines were used to examine the cell proliferation suppressive effect in vitro using inhibitors of mir-18a, 95, 221, and 330, which are upregulated in cancer tissues. The results showed that mir-330 inhibitor had a high ability to inhibit cell proliferation in all of the cell lines. In addition, in order to identify the genes targeted by mir-330, we focused on the tumor suppressor genes PTPN9 and SPRY2 and performed mRNA expression analysis. The mRNA expression level of PTPN9 was significantly increased in all cells compared to the control group. On the other hand, although the expression level of SPRY2 was increased in all cells, the change in expression was not significant. Furthermore, the mRNA expression levels of apoptosis-related markers increased after the addition of mir-330 inhibitor. Mir-330 inhibitor was suggested to induce apoptosis in canine prostate cancer cells through regulation of PTPN9 expression.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではmir-330が癌抑制遺伝子であるPTPN9の発現調節を通じて、犬前立腺癌の増殖に寄与することを示唆した。これらの知見は未だ著効を示す治療が確立されていない犬前立腺癌に対するmir-330またはPTPN9を標的とした新たな分子標的治療戦略の基盤をなすだけでなく、同様の制御機構をもつ癌治療に対しても有益な知見を提供しうるものであり社会的な意義があるだろう。
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