期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/srep44543
关键词
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资金
- National Natural Science Foundation of China [81502523]
- Shanghai Committee of Science and Technology [16DZ2280900, 16DZ2280990]
- Ministry of Science and Technology of China [2016YFC0905300]
- Zhejiang Provincial Natural Science Foundation of China [LY15H160058]
- Zhejiang Provincial Medical Technology Science Project [2015KYB245]
The molecular mechanisms underlying colorectal cancer (CRC) development remain elusive. In this study, we examined the miRNA and mRNA expressions in the adenoma-carcinoma sequence (ACS), a critical neoplastic progression in CRC development. We found that miR-137 was down-regulated in all adenoma and carcinoma tissues. Low miR-137 levels were correlated negatively with tumor progression and metastasis. Then we identified the inhibition effect of the miR-137 in CRC development, both in CRC cell lines and mouse models. MiR-137 was shown to control CRC cell proliferation, colony formation, migration and invasion and to control tumor growth and metastasis. We further confirmed the negative association between miR-137 and c-Met expression and thus validated this important oncogene as the target of miR-137 in CRC. In addition, we found a DNA methyl-CpG-binding protein, Mecp2, was upregulated in ACS tissues via mRNA sequencing. Further experiment showed that miR-137 expression in CRC was subjected to epigenetic regulation mediated by Mecp2. We also confirmed c-Met expression can be up-regulated by silencing of miR-137 and suppressed by coexpression of Mecp2 and miR-137. These findings highlight the critical role of miR-137-c-Met nexus in CRC development and reveal Mecp2-regulated epigenetic silence causes the downregulation of miR-137 in colorectal adenoma and carcinoma.
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