A translational research on miR-224: towards novel diagnostic and therapeutic approach for hepatocellular carcinoma

• Project/Area Number: 24590953
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Yamagata University
• Principal Investigator: SHO Ri 山形大学, 医学(系)研究科(研究院), 助教 (80344787)
• Co-Investigator(Kenkyū-buntansha): WATANABE Hisayoshi 山形大学, 医学部, 講師 (00332536) ; ISHII Rika 山形大学, 医学部, 助教 (60466612) ; ZHANG Xuhong 山形大学, 大学院医学系研究科, 助教 (10292442)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 肝癌 / microRNA / 分子標的治療 / 診断マーカー / 肝がん

Outline of Final Research Achievements

Our previous study has determined that aberrant expression of miR-224 in hepatocellular carcinoma (HCC) was associated with cancer cell invasion. Using mouse xenograft model, we further investigated whether miR-224 could serve as a potential target for HCC therapy. Inoculation of HCC cells transfected with miR-224 inhibitor (antagomiR-224) into subcutaneous of athymic nude mice revealed that inhibition of miR-224 in HCC cells significantly delayed tumor formation as compared to control. Direct intratumoral injection of antagomiR-224 didn’t cause tumor regression, but did show a delay in tumor growth in comparison to mice treated with control substance, suggesting that miR-224 may serve as a potential therapeutic target in HCC.

Research Products

• [Journal Article] Applying data envelopment analysis to preventive medicine: a novel method for constructing a personalized risk model of obesity (2015)
  • Author(s): Narimatsu H, Nakamura S, Sho R, et al
  • Journal Title: PLoS One Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Applying spatial epidemiology to hematological disease using R: a guide for hematologists and oncologists (2014)
  • Author(s): Kohno K, Narimatsu H, Sho R, et al
  • Journal Title: J Blood Med Volume: 5 Pages: 31-36
  • DOI: 10.2147/jbm.s57944
  • Peer Reviewed / Open Access
• [Journal Article] Transmission of Hepatitis C Virus From a Mother to a Child Carrying IL28B Heterozygote rs8099917 Among Three Brothers: A Long-Term Follow-Up (2014)
  • Author(s): Saito T, Mizuno K, Shao L, et al
  • Journal Title: J Med Cases Volume: 5 Pages: 227-231
  • DOI: 10.14740/jmc1736w
  • Peer Reviewed / Open Access
• [Journal Article] Dynamics of serum metabolites in patients with chronic hepatitis C receiving pegylated interferon plus ribavirin: A metabolomics analysis (2013)
  • Author(s): Saito, T., Sugimoto, M., Igarashi, K., Saito, K., Shao, L., Katsumi, T., Tomita, K., Sato, C., Ishii, R., Okumoto, K., Nishise, Y., Watanabe, H., Tomita, M., Ueno, Y., Soga, T.
  • Journal Title: Metabolism Volume: 62 Issue: 11 Pages: 1577-1586
  • DOI: 10.1016/j.metabol.2013.07.002
  • Peer Reviewed
• [Journal Article] Serum prolactin levels and prolactin mRNA expression in peripheral blood mononuclear cells in hepatitis C virus infection (2013)
  • Author(s): Ishii R, Saito T, Shao L, et al
  • Journal Title: J Med Virol Volume: 85 Issue: 7 Pages: 1199-1205
  • DOI: 10.1002/jmv.23599
  • Peer Reviewed
• [Journal Article] Constructinga contemporary gene-environmental cohort: study design of the Yamagata Molecular Epidemiological Cohort Study (2013)
  • Author(s): Yamagata University Genomic CohortConsortium. Tamiya G、UekiM, 他57名
  • Journal Title: J Hum Genet Volume: 58(1) Issue: 1 Pages: 54-56
  • DOI: 10.1038/jhg.2012.128
  • Peer Reviewed
• [Journal Article] Relationship between dietary intake and microalbuminuria: findings from the Takahata study (2012)
  • Author(s): Sato M, Hozawa A, Konta T, Shao L et al
  • Journal Title: Clin Exp Nephrol Volume: 16 Issue: 1 Pages: 147-55
  • DOI: 10.1007/s10157-011-0539-5
  • NAID: 10030343218
  • Peer Reviewed
• [Presentation] Genetic polymorphism in interferon-λ4 gene and treatment response to peginterferon and ribavirin in Japanese chronic hepatitis C (2014)
  • Author(s): Watanabe H, Sho R, Saito T, et al
  • Organizer: 65th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: John B. Hynes Veterans Memorial Convention Center, Boston
  • Year and Date: 2014-11-07 – 2014-11-11
• [Presentation] ヒト肝癌細胞異種移植モデルを用いたantagomiR-224の抗腫瘍活性の検討 (2014)
  • Author(s): 邵力,張旭紅, 福田直樹 等
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館・グランドプリンスホテル京都, 京都
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] 歯肉癌患者血漿を用いた網羅的解析により発見したmiR-223の機能解析と臨床的有用性の検討 (2014)
  • Author(s): 橘寛彦, 邵力, 武田裕司 等
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜, 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 日本人C型肝炎患者におけるインターフェロンλ4遺伝子多型性の検討 (2014)
  • Author(s): 渡辺久剛, 邵力, 上野義之
  • Organizer: 第100回日本消化器病学会総会
  • Place of Presentation: 東京国際フォーラム, 東京
  • Year and Date: 2014-04-23 – 2014-04-26
• [Presentation] Is microRNA-224 a potential therapeutic target for HCC? (2013)
  • Author(s): Zhang XH, Sho R, Watanabe H, et al
  • Organizer: 第86回日本生化学会
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] The Use of RNAi-based Screens to Identify Host Factors Involved in HCV Replication (2012)
  • Author(s): Sho R, Zhang XH, Watanabe H, et al
  • Organizer: The 10th JSH Single Topic Conference “Hepatitis C:Best Practice Based on Science”
  • Place of Presentation: KEIO PLAZA HOTEL (Shinjuku, Tokyo)
• [Presentation] Identification of miR-224 target genes and pathways related to hepatocellular carcinoma (2012)
  • Author(s): Zhang XH, Sho R, Watanabe H, et al
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場 (福岡)