title: Mecp2-mediated Epigenetic Silencing of miR-137 Contributes to Colorectal Adenoma-Carcinoma Sequence and Tumor Progression via Relieving the Suppression of c-Met.
abstract: 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.
authors.affiliation: Endoscopy center, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.|Endoscopy Research Institute of Fudan University, Shanghai, 200032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Endoscopy center, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.|Endoscopy Research Institute of Fudan University, Shanghai, 200032, China.
authors.forename: Shi-Lun
authors.initials: SL
authors.lastname: Cai
authors.affiliation: Endoscopy center, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.|Endoscopy Research Institute of Fudan University, Shanghai, 200032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Endoscopy center, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.|Endoscopy Research Institute of Fudan University, Shanghai, 200032, China.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Qi
authors.affiliation: Endoscopy center, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.|Endoscopy Research Institute of Fudan University, Shanghai, 200032, China.
authors.forename: Xu-Quan
authors.initials: XQ
authors.lastname: Li
authors.affiliation: Department of Oncological Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
authors.forename: Le-Chi
authors.initials: LC
authors.lastname: Ye
authors.affiliation: Department of Pathology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Xie
authors.affiliation: Department of Pathology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
authors.forename: Ying-Yong
authors.initials: YY
authors.lastname: Hou
authors.affiliation: Endoscopy center, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.|Endoscopy Research Institute of Fudan University, Shanghai, 200032, China.
authors.forename: Li-Qing
authors.initials: LQ
authors.lastname: Yao
authors.affiliation: Endoscopy center, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.|Endoscopy Research Institute of Fudan University, Shanghai, 200032, China.
authors.forename: Mei-Dong
authors.initials: MD
authors.lastname: Xu
authors.affiliation: Endoscopy center, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.|Endoscopy Research Institute of Fudan University, Shanghai, 200032, China.
authors.forename: Ping-Hong
authors.initials: PH
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Xu
authors.affiliation: Endoscopy center, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.|Endoscopy Research Institute of Fudan University, Shanghai, 200032, China.
authors.forename: Yun-Shi
authors.initials: YS
authors.lastname: Zhong
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000473:pathology; D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: C497392:MECP2 protein, human; C545567:MIRN137 microRNA, human; D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs; D019859:Proto-Oncogene Proteins c-met