2018 Fiscal Year Annual Research Report
miR-137 Regulates the Tumorigenicity of Colon Cancer Stem Cells through the Inhibition of DCLK1
| Project/Area Number |
16K10539
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| Research Institution | Kyoto University |
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Principal Investigator |
久森 重夫 京都大学, 医学研究科, 助教 (50534351)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 大腸癌幹細胞 / DCLK1 / 正常大腸幹細胞 |
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| Outline of Annual Research Achievements |
Background and Objectives: microRNAs (miRNAs) are important regulators of cancer stem cell (CSC) properties and are considered to be a potential therapeutic target. However, few studies have focused on miRNAs which are specifically related to colon CSC. Recently, doublecortine-like kinase 1(DCLK1) has been proposed to be a distinctive marker for colon CSCs. In this study, we showed miRNA-137 (miR-137) targets DCLK1 and unveiled the role of the miR-137/DCLK1 axis in colon CSC properties.
Results: miR-137 expression was downregulated in the colon CSC population, while DCLK1 was highly expressed. miR-137 was shown to suppress the activity of the luciferase gene linked to the 3’UTR of DCLK1, and the expression of DCLK1 protein. The transduction of exogenous miR-137 suppressed the organoid growth of colon cancer cells as well as shRNAs against DCLK1. The defect in organoid growth by the transduction of miR-137 or shRNAs were substantially rescued by coexpression of the exogenous DCLK1. Although miR-137 overexpression did not affect the organoid development of the normal intestine, miR-137 knockdown promoted the organoid development of normal colon cells. Xenograft tumor formation was markedly suppressed in the miR-137-transduced SW480 cell-injected mice.
Conclusion: These results suggest that miR-137 has the potential to suppress the tumorigenicity of
colon CSCs through the inhibition of DCLK1.
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