Elucidation of the miRNA-EZH2 feedback loop regulating endometrial cancer microenvironment
Project/Area Number |
16K11123
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Hokkaido University |
Principal Investigator |
Konno Yosuke 北海道大学, 医学研究院, 助教 (10572703)
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Co-Investigator(Kenkyū-buntansha) |
董 培新 北海道大学, 医学研究院, 助教 (50602504)
櫻木 範明 北海道大学, 医学研究院, 名誉教授 (70153963)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | microRNA / 子宮体癌 / EZH2 / EMT / 癌 / 遺伝子 |
Outline of Final Research Achievements |
In this study, we aimed to clarify whether the miRNA-EZH2 feedback loop contributes to EZH2 overexpression in endometrial cancer and whether EZH2 induces the expression of IL-6/8 through miRNAs-mediated signaling pathways. We found that EZH2 and tumor suppressor miRNAs mutually form a negative feedback loop, resulting in enhanced expression of EZH2 and decreased expression of tumor suppressor miRNAs and that EZH2 induces the overproduction of IL-6/8 via miRNAs-mediated pathways in endometrial cancer cells. These findings suggest that targeting and inhibition of EZH2 represents a potential therapeutic strategy for endometrial cancer.
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Academic Significance and Societal Importance of the Research Achievements |
EZH2と癌抑制miRNA群が相互に負のフィードバックループを形成して、EZH2の発現亢進及びlet-7bなどのmiRNAの発現低下を招き、下流にあるTwist、Snail、STAT3経路、NF-κB経路及びWnt/β-catenin経路の活発化を介して、IL-6/8過剰産生及び体癌の悪性化を導くという重要な成果が得られている。本研究により得られた知見は、今後体癌の根絶を目指す基層研究の発展及び新しい治療法の開発に大きく貢献していると考えられる。
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Report
(4 results)
Research Products
(39 results)
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[Journal Article] EZH2 inhibition suppresses endometrial cancer progression via miR-361/Twist axis.2017
Author(s)
Ihira K, Dong P, Xiong Y, Watari H, Konno Y, Hanley S-JB, Noguchi M, Hirata N, Suizu F, Yamada T, Kudo M, and Sakuragi N.
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Journal Title
Oncotarget
Volume: 8 (8)
Issue: 8
Pages: 13509-13520
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] KLF4 expression enhances the efficacy of chemotherapy drugs in ovarian cancer cells2017
Author(s)
Wang B, Shen A, Ouyang X, Zhao G, Du Z, Huo W, Zhang T, Wang Y, Yang C, Dong P, Watari H, Pfeffer LM, Yue J
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Journal Title
Biochem Biophys Res Commun
Volume: 484
Issue: 3
Pages: 486-492
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells2017
Author(s)
Huo W, Zhao G, Yin J, Ouyang X, Wang Y, Yang C, Wang B, Dong P, Wang Z, Watari H, Chaum E, Pfeffer LM, Yue J
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Journal Title
J Cancer
Volume: 8
Issue: 1
Pages: 57-64
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphere-forming ability of ovarian cancer cells2016
Author(s)
Dong P, Xiong Y, Watari H, Hanley SJ, Konno Y, Ihira K, Yamada T, Kudo M, Yue J, Sakuragi N
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Journal Title
J Exp Clin Cancer Res
Volume: 5
Issue: 1
Pages: 132-141
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Suppression of iASPP-dependent aggressiveness in cervical cancer through reversal of methylation silencing of microRNA-1242016
Author(s)
Dong P, Xiong Y, Watari H, Hanley SJ, Konno Y, Ihira K, Suzuki F, Yamada T, Kudo M, Yue J, Sakuragi N
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 35480-35491
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Evaluation of partial genotyping with HPV 16/18 for triage of HPV positive cytology negative Japanese women: Baseline results of the COMPACT study2018
Author(s)
Aoyama-Kikawa S, Fujita H, Hanley SJB, Kasamo M, Kikuchi K, Torigoe T, Matsuno Y, Tamakoshi A, Sasaki T, Matsuura M, Kato Y,Dong P, Watari H, Saito T, Sengoku K, Sakuragi N
Organizer
The 32nd International Papillomavirus Conference, Sydney (Australia)
Related Report
Int'l Joint Research
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[Presentation] Comparison of HPV genotyping and cytology triage, COMPACT-Study: Design, methods and baseline results in 14,642 women2018
Author(s)
3.Aoyama-Kikawa S, Fujita H, Hanley SJB, Kasamo M, Kikuchi K, Torigoe T, Matsuno Y, Tamakoshi A, Sasaki T, Matsuura M, Kato Y, Dong P, Watari H, Saito T, Sengoku K, Sakuragi N
Organizer
The 32nd International Papillomavirus Conference, Sydney (Australia)
Related Report
Int'l Joint Research
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