| Project/Area Number |
18K09278
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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 56040:Obstetrics and gynecology-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
DONG PEIXIN 北海道大学, 医学研究院, 特任助教 (50602504)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 子宮頸癌 / PD-L1 / microRNA / miRNA / Endometrial cancer |
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| Outline of Final Research Achievements |
PD-L1, a key inhibitory immune receptor, has crucial functions in cancer immune evasion, but whether PD-L1 promotes the malignant properties of cervical cancer (CC) cells and the mechanism by which PD-L1 is regulated in CC remains unclear. We report that PD-L1 is overexpressed in CC, and shRNA-mediated PD-L1 depletion suppresses the proliferation, invasion, and tumorigenesis of CC cells. Loss of miR-140/142/340/383 contributes to PD-L1 upregulation. We also showed that miR-18a enhances PD-L1 levels by targeting PTEN, WNK2 (ERK1/2 pathway inhibitor), and SOX6 (Wnt/β-catenin pathway inhibitor and p53 pathway activator) to activate the PI3K/AKT, MEK/ERK, and Wnt/β-catenin pathways and inhibit the p53 pathway. Our data implicate PD-L1 as a novel oncoprotein and indicate that miR-140/142/340/383 and miR-18a are key upstream regulators of PD-L1 and potential targets for CC treatment.
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| Academic Significance and Societal Importance of the Research Achievements |
近年若い世代の子宮頸癌（頸癌）発生率が急増し、20～30歳代においては、婦人科悪性腫瘍の中で最も頻度の高い癌である。頸癌転移の制御は未だ満足できる状況ではなく、患者の死亡の最大の原因となる。頸癌の進展に関わる分子基盤は十分には理解されておらず、依然として有望な創薬標的分子の同定は急務である。本研究でPD-L1遺伝子は頸癌細胞の悪性形質を促進する作用があることが判明した。今後PD-L1を用いた新規頸癌治療法の開発は、頸癌に対する新しい治療戦略の構築に有効である可能性を示している。
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