Detection of aberrant expression of microRNAs and development of new diagnostics and treatment in lung cancer

• Project/Area Number: 23592061
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Okayama University
• Principal Investigator: MIYOSHI Shinichiro 岡山大学, 医歯(薬)学総合研究科, 教授 (00190827)
• Co-Investigator(Kenkyū-buntansha): TOYOOKA Shinichi 岡山大学, 大学院医歯薬学総合研究科, 教授 (30397880) ; SOH Junichi 岡山大学, 岡山大学病院, 助教 (90559890) ; TSUKUDA Kazunori 岡山大学, 岡山大学病院, 講師 (20346430) ; ASANO Hiroaki 岡山大学, 岡山大学病院, 助教 (70534775)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 原発性肺癌 / マイクロRNA

Research Abstract

We detected that expression of miR-34b/c and miR-200c was inhibited in lung cancer. miR-34b/c was more frequently inhibited by methylation in small cell lung cancer. We detected that induction of miR-34b/c showed anti-tumor effect in malignant pleural mesothelioma in vivo. As for miR-200c, its expression was maintained in EGFR-mutant lung cancer cell lines and it was inhibited in EGFR-mutant lung cancer cell line with acquired resistance to EGFR-tyrosine kinase inhibitor (TKI). In addition, epithelial to mesenchymal transition (EMT) was observed in that TKI-resistant cell line. We also confirmed that induction of miR-200c to the TKI-resistant cell line resulted in the termination of EMT.

Research Products

• [Journal Article] Myeloid cell-derived soluble IL-6 receptor diminishes the differentiation of tumor-specific Th1 cells to exacerbate tumor progression (2017)
  • Author(s): Shinojima N, Hossain A, Takezaki T, Fueyo J, Gumin J, Gao F, Nwajei F, Marini FC, Andreeff M, Kuratsu J, Lang FF.
  • Journal Title: Cancer Res. Volume: 73(7) Pages: 1311-1318
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Preclinical evaluation of microRNA-34b/c deliverly for malignant pleural mesothelioma (2014)
  • Author(s): Ueno T, Toyooka S, Fukazawa T, Kubo T, Soh J, Asano H, Muraoka T, Tanaka N, Maki Y, Shien K, Furukawa M, Sakaguchi M, Yamamoto H, Tsukuda K, Miyoshi S
  • Journal Title: Acta Med Okayama Volume: 68(1) Pages: 23-26
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24553485
  • Peer Reviewed
• [Journal Article] Preclinical evaluation of microRNA-34b/c delivery for malignant pleural mesothelioma. (2014)
  • Author(s): Ueno T, Toyooka S, Fukazawa T, Kubo T, Soh J, Asano H, Muraoka T, Tanaka N, Maki Y, Shien K, Furukawa M, Sakaguchi M, Yamamoto H, Tsukuda K, Miyoshi S.
  • Journal Title: Acta Med Okayama Volume: 68 Pages: 23-26
  • NAID: 120005372648
  • Peer Reviewed
• [Journal Article] The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma (2013)
  • Author(s): Muraoka T, Soh J, Toyooka S, Aoe K, Fujimoto N, Hashida S, Maki Y, Tanaka N, Shien K, Furukawa M, Yamamoto H, Asano H, Tsukuda K, Kishimoto T, Otsuki T, Miyoshi S
  • Journal Title: Lung Cancer Volume: 82(3) Pages: 485-490
  • DOI: 10.1016/j.lungcan.2013.09.017
  • NAID: 120005367626
  • Peer Reviewed
• [Journal Article] Downregulation of microRNA-34 induces cell proliferation and invasion of human mesothelial cells. (2013)
  • Author(s): Tanaka N, Toyooka S, Soh J, Tsukuda K, Shien K, Furukawa M, Muraoka T, Maki Y, Ueno T, Yamamoto H, Asano H, Otsuki T, Miyoshi S
  • Journal Title: Oncology Reports Volume: 29(6) Pages: 2169-2174
  • DOI: 10.3892/or.2013.2351
  • Peer Reviewed
• [Journal Article] Acquired resistance to EGFR inhibitors is associated with a manifestation of stem cell-like properties in cancer cells (2013)
  • Author(s): Shien K, Toyooka S, Yamamoto H, Soh J, Jida M, Thu KL, Hashida S, Maki Y, Ichihara E, Asano H, Tsukuda K, Takigawa N, Kiura K, Gazdar AF, Lam WL, Miyoshi S.
  • Journal Title: Cancer Res Volume: 73 Pages: 3051-3061
  • DOI: 10.1158/0008-5472.can-12-4136
  • Peer Reviewed
• [Journal Article] Frequent methylation and oncogenic role of microRNA-34b/c in small-cell lung cancer. (2012)
  • Author(s): Tanaka N, Toyooka S, Soh J, Kubo T, Yamamoto H, Maki Y, Muraoka T, Shien K, Furukawa M, Ueno T, Asano H, Tsukuda K, Aoe K, Miyoshi S
  • Journal Title: Lung Cancer Volume: 76(1) Pages: 32-8
  • DOI: 10.1016/j.lungcan.2011.10.002
  • NAID: 120005311982
  • Peer Reviewed
• [Presentation] Acquisition of stem cell-like properties during acquired resistance to epidermal growth factor receptor inhibitors (2013)
  • Author(s): Shien K, Toyooka S, Yamamoto H, Soh J, Thu KL, Hashida S, Maki Y, Ichihara E, Asano H, Tsukuda K, Takigawa N, Kiura K, Gazdar AF, Lam WL, Miyoshi S
  • Organizer: AACR Annual Meeting 2013
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2013-04-09
• [Presentation] Down-regulation of microRNA-34 induces cell proliferation and invasion of human mesothelial cells (2012)
  • Author(s): Tanaka N, Toyooka S, Soh J, Tsukuda K, Shien K, Furukawa M, Muraoka T, Maki Y, Ueno T, Asano H, Otsuki T, Miyoshi S
  • Organizer: 103rd AACR Annual Meeting
  • Place of Presentation: Chicago, USA
  • Year and Date: 2012-04-01
• [Presentation] 小細胞肺癌におけるmicroRNA-34b/cのメチル化とその役割 (2011)
  • Author(s): 田中則光、豊岡伸一、宗淳一、浅野博昭、佃和憲、三好新一郎
  • Organizer: 日本癌治療学会総会
  • Place of Presentation: 名古屋
• [Presentation] 小細胞肺癌におけるmicroRNA-34b/cのメチル化とその役割 (2011)
  • Author(s): 田中則光、豊岡伸一、宗淳一、浅野博昭、佃和憲、三好新一郎
  • Organizer: 日本癌治療学会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Down-regulation of microRNA-34 induces cell proliferation and invasion of human mesothelial cells.
  • Author(s): Tanaka N, Toyooka S, Soh J, Tsukuda K, Shien K, Furukawa M, Muraoka T, Maki Y, Ueno T, Asano H, Otsuki T, Miyoshi S.
  • Organizer: 103rd AACR Annual Meeting
  • Place of Presentation: Chicago, USA
• [Remarks]
  • URL: http://www.nigeka-okayama-u.jp