Mecp2-mediated Epigenetic Silencing of miR-137 Contributes to Colorectal Adenoma-Carcinoma Sequence and Tumor Progression via Relieving the Suppression of c-Met
Autor: | Yingyong Hou, Zhi-Peng Qi, Xiao-Feng Xie, Ping-Hong Zhou, Xu-Quan Li, Le-chi Ye, Mei-Dong Xu, Shi-Lun Cai, Yun-Shi Zhong, Jian Li, Tao Chen, Li-Qing Yao, Jianmin Xu |
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Rok vydání: | 2017 |
Předmět: |
Adenoma
0301 basic medicine C-Met Methyl-CpG-Binding Protein 2 Colorectal adenoma Biology Article Epigenesis Genetic Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement microRNA medicine Animals Humans Gene silencing Neoplasm Invasiveness Neoplasm Metastasis Cell Proliferation Genetics Multidisciplinary Oncogene Carcinoma Proto-Oncogene Proteins c-met HCT116 Cells medicine.disease Xenograft Model Antitumor Assays digestive system diseases Gene Expression Regulation Neoplastic MicroRNAs mir-137 030104 developmental biology MRNA Sequencing chemistry Tumor progression 030220 oncology & carcinogenesis Cancer research Colorectal Neoplasms |
Zdroj: | Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/srep44543 |
Popis: | 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 up-regulated 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. |
Databáze: | OpenAIRE |
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