Identification of sarcopenia-related microRNAs causing poor prognosis in sarcopenia patients with gastrointestinal cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23922
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Kiuchi Jun 京都府立医科大学, 医学部附属病院, 専攻医 (10847180)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 胃癌 / 大腸癌 / サルコペニア / 癌抑制型microRNA / エクソソーム / エクササイズ

Outline of Final Research Achievements

Previous reports have been showed that presence of sarcopenia had been associated with poor prognosis in patients with gastrointestinal cancers. Then, we analyzed the background mechanism causing poor prognosis in cancer patients with sarcopenia. First, we identified miR-133b, which was derived from skeletal muscle, as a plasma biomarker reflecting sarcopenia. Next, we confirmed tumor suppressive functions of miR-133b using gastric cancer cell lines. Then, we clarified that miR-133b was released from skeletal muscle to systemic circulation by incorporated in exosomes and functioned as a tumor suppressive molecule by picked up into cancer cells. Finally, we showed that exercising kept skeletal muscle volume and high levels of plasma miR-133b resulting in suppression of cancer progression in mice which was transplanted gastric cancer cells.

Free Research Field

消化器癌における癌抑制型microRNAの治療応用

Academic Significance and Societal Importance of the Research Achievements

高齢化社会において、サルコペニア併存症例は今後ますます増加することが予想され、このような症例の不良な予後を改善する治療戦略の確立が喫緊の課題である。本研究において、miR-133bがサルコペニア併存消化器癌患者の不良な予後に重大な影響を及ぼしている可能性があり、運動療法やmiR-133bの直接投与により血中miR-133b濃度を維持することが、サルコペニア併存担癌患者の予後を改善する可能性があることが分かった。これはサルコペニア併存担癌患者に対する治療戦略として、新たな可能性を示すものである。