| Project/Area Number |
18K15803
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 大腸癌幹細胞 / エクソソーム / 大腸癌 |
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| Outline of Final Research Achievements |
Exosomes are membrane-enclosed nanovesicles and have been increasingly recognized as important cell communications by transmitting microRNA (miRNA).Development of a three-dimensional organoid culture system allows us to perform long-term expansion of epithelial organoids of human CRA and CRC. We established six CRC patient-derived organoids and eight CRA patient-derived organoids. We analyzed the exosomal and cellular microRNA expression profiles by miRNA microarray. We found different miRNA expression profiles between CRC- and CRA-derived organoids, and that both exosomal and cellular miR-1246 expression was upregulated in CRC-derived organoids compared to CRA-derived organoids. Alteration of miR-1246 expression by miR-1246 mimic or inhibitor accordingly increased or decreased cell proliferation in HT-29 CRC cell line, respectively. In conclusion, we here reported upregulation of miR-1246 might play a role in increased cell proliferation in colorectal adenoma-carcinoma transition.
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| Academic Significance and Societal Importance of the Research Achievements |
３次元オルガノイド培養システムからエクソソームを抽出した。オルガノイド培養上清から抽出可能という知見は新規である。また、腫瘍の進行度によりエクソソームの性質が異なることを明らかとした。されにはニッチ形成に関与していることも明らかとした。大腸癌が発育にともない、癌は周囲の細胞、もしくは自身のheterogeneityに適応するために分泌している可能性が推定され、大腸癌の発育進展の機序解明に重要な知見がえられた。
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