Analysis of microRNA in cancer microenvironment involved in colorectal liver metastasis

• Project/Area Number: 17K10635
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Yamaguchi University
• Principal Investigator: IIDA Michihisa 山口大学, 大学院医学系研究科, 助教 (50554797)
• Co-Investigator(Kenkyū-buntansha): 硲 彰一 山口大学, 医学部, 教授(寄附講座等) (50253159) ; 坂本 和彦 山口大学, 医学部附属病院, 講師 (50420526) ; 鈴木 伸明 山口大学, 大学院医学系研究科, 講師 (50526910)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 大腸癌 / 癌間質 / miRNA / 肝転移 / 癌微小環境 / microRNA

Outline of Final Research Achievements

As a result of comprehensive analysis by miRNA array, miR221 and miR222 were significantly higher in the primary cancerous interstitium of colorectal cancer with liver metastasis than in the cases of colorectal cancer without liver metastasis.Expression analysis by qPCR revealed that liver metastasis, distant metastasis, and vascular invasion were high in the miR221 high expression group, and overall survival was poor. Similarly, liver metastasis, distant metastasis, and overall survival were high in the miR222 high expression group. The duration was poor. Meanwhile, there was no significant correlation between miR221 and miR222 expression in cancer cells and clinicopathologic factors. Expression analysis by ISH showed strong miR221 and miR222 expression in the cytoplasm of cancer cells and fibroblasts in liver metastases.

Academic Significance and Societal Importance of the Research Achievements

大腸癌原発巣の間質においてmiR221およびmiR222の高発現は、大腸癌の進展とくに肝転移および遠隔転移に関与することが示された。このことは大腸癌の予後に最も関与する遠隔転移が起こる過程が新たに示された可能性がある。また癌間質のなかでも特に線維芽細胞においてmiR221およびmiR222の高発現が示されたことは、癌の進展や転移に関わるとされる癌関連線維芽細胞の発生の過程にもmiR221およびmiR222の高発現が関与することが示唆されており、癌関連線維芽細胞の制御という面でも意義深いと考えられる。

Research Products

• [Journal Article] Overexpression of miR221 and miR222 in the cancer stroma is associated with malignant potential in colorectal cancer (2018)
  • Author(s): Iida Michihisa、Hazama Shoichi、Tsunedomi Ryouichi、Tanaka Hironori、Takenouchi Hiroko、Kanekiyo Shinsuke、Tokumitsu Yukio、Tomochika Shinobu、Tokuhisa Yoshihiro、Sakamoto Kazuhiko、Suzuki Nobuaki、Takeda Shigeru、Ueno Tomio、Yamamoto Shigeru、Yoshino Shigefumi、Fujita Koji、Kuroda Masahiko、Nagano Hiroaki
  • Journal Title: Oncology Reports Volume: 40 Pages: 1621-1631
  • DOI: 10.3892/or.2018.6575
  • Peer Reviewed / Open Access
• [Presentation] 癌間質におけるmiR221およびmiR222の過剰発現は大腸癌の悪性度と相関する (2017)
  • Author(s): 飯田 通久
  • Organizer: 第26回日本がん転移学会