Functional analysis of small RNAs involved in tumorigenesis of a new molecular subtype of colorectal cancer, and investigation of their new molecular targets

• Project/Area Number: 15K08962
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: TAKAHASHI MASANOBU 東北大学, 加齢医学研究所, 准教授 (00447161)
• Research Collaborator: TAKAHASHI Hidekazu 石巻赤十字病院, 腫瘍内科, 医師 ; KOBAYASHI Akihiro 東北大学, 加齢医学研究所, 大学院生
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: miRNA / BRAF / 抗EGFR抗体 / 大腸がん / BRAF変異 / 大腸癌

Outline of Final Research Achievements

This study was aimed to identify specific miRNAs, a class of small RNAs, that could be involved in oncogenesis of a molecular subgroup, BRAF-mutated colorectal cancer, and clarify biological functions of the miRNAs. A genome-wide miRNA expression analysis and functional analysis using colorectal cancer cell lines revealed that a miRNA, significantly down-regulated in BRAF-mutated colorectal cancer, acts as a tumor suppressor and affects sensitivity to anti-EGFR therapy in colorectal cancer. We are now investigating the mechanism underlying the dysregulation of this miRNA and analyzing the miRNA-involving signaling pathways that may relate to the carcinogenesis and/or chemosensitivity. The results could lead to further developing novel targeted therapies of colorectal cancer.

Research Products

• [Journal Article] microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer. (2017)
  • Author(s): Takahashi, H.，Takahashi, M.，Ohnuma, S.，Unno, M.，Yoshino, Y.，Ouchi, K.，Takahashi, S.，Yamada, Y.，Shimodaira, H.，Ishioka, C.:
  • Journal Title: BMC Cancer Volume: 17 Issue: 1 Pages: 723-727
  • DOI: 10.1186/s12885-017-3739-x
  • Peer Reviewed / Open Access
• [Journal Article] The G8 screening tool enhances prognostic value to ECOG performance status in elderly cancer patients: A retrospective, single institutional study. (2017)
  • Author(s): Takahashi M, Takahashi M, Komine K, Yamada H, Kasahara Y, Chikamatsu S, Okita A, Ito S, Ouchi K, Okada Y, Imai H, Saijo K, Shirota H, Takahashi S, Mori T, Shimodaira H, Ishioka C.
  • Journal Title: PLoS One. Volume: 12(6) Issue: 6 Pages: e0179694-e0179694
  • DOI: 10.1371/journal.pone.0179694
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Efficacy and safety of gemcitabine plus docetaxel in Japanese patients with unresectable or recurrent bone and soft tissue sarcoma: Results from a single-institutional analysis. (2017)
  • Author(s): Takahashi M, Komine K, Imai H, Okada Y, Saijo K, Takahashi M, Shirota H, Ohori H, Takahashi S, Chiba N, Mori T, Shimodaira H, Ishioka C.
  • Journal Title: PLoS One. Volume: 12(5) Issue: 5 Pages: e0176972-e0176972
  • DOI: 10.1371/journal.pone.0176972
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Efficacy and safety of denosumab versus zoledronic acid in delaying skeletal-related events in patients with gastrointestinal cancer, pancreas-biliary system cancer, and other rare cancers. (2017)
  • Author(s): Imai H, Saijo K, Yamada H, Ohuchi K, Okada Y, Komine K, Takahashi M, Takahashi S, Takahashi M, Shimodaira H, Ishioka C.
  • Journal Title: J Bone Oncol Volume: 6 Pages: 37-40
  • Peer Reviewed
• [Journal Article] DNA methylation status as a biomarker of anti-epidermal growth factor receptor treatment for metastatic colorectal cancer. (2015)
  • Author(s): Ouchi K, Takahashi S, Yamada Y, Tsuji S, Tatsuno K, Takahashi H, Takahashi N, Takahashi M, Shimodaira H, Aburatani H, Ishioka C.
  • Journal Title: Cancer Science Volume: 106 Issue: 12 Pages: 1722-1729
  • DOI: 10.1111/cas.12827
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Functional Complementation Assay for 47 MUTYH Variants in a MutY-Disrupted Escherichia coli Strain. (2015)
  • Author(s): Komine K, Shimodaira H, Takao M, Soeda H, Zhang X, Takahashi M, Ishioka C.
  • Journal Title: Human Mutation Volume: 36 Issue: 7 Pages: 704-711
  • DOI: 10.1002/humu.22794
  • Peer Reviewed / Int'l Joint Research
• [Presentation] microRNA-193a-3p acts as a tumor suppressor in BRAF-mutated colorectal cancer (2016)
  • Author(s): 1.Takahashi H, Takahashi M, Takahashi S, Shimodaira H, Ishioka, C
  • Organizer: AACR Annual Meeting 2016
  • Place of Presentation: New Orleans, USA
  • Int'l Joint Research
• [Funded Workshop] AACR Annual Meeting 2016 (2016)
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2016-04-16