title: Epigenetic silencing of miR-137 contributes to early colorectal carcinogenesis by impaired Aurora-A inhibition.
abstract: MicorRNA-137 is silenced in human colorectal cancer tissues and colon polyps. Our study showed that the decreased expression of miR-137 is significantly different in various types of polyp which maintain different potentials to lead to CRC development. The expression of miR-137 gradually decreases during the process of colorectal carcinogenesis. Receiver operating characteristic curve (ROC) analysis indicates that the loss of miR-137 expression in colon polyps can serve as a biomarker to predict the predisposition of colorectal carcinogenesis. By cell model and xenograft animal model, the enforced expression of miR-137 in colorectal cancer cells can inhibit cell proliferation and tumor formation, induce G2/M arrest, and lead to apoptosis. The expression pattern of miR-137 and Aurora-A or PTGS2 is negatively correlated in human colorectal cancer tissues and colon polyps. Those effects induced by overexpressed miR-137 can be rescued by the overexpression of Aurora-A. In summary, our study suggests that the loss of miR-137 expression in colon polyps can serve as a biomarker to predict the tendency toward to CRC formation through the impaired inhibitory effect of Aurora-A. The investigation of the regulatory mechanism of miR-137-mediated Aurora-A inhibition may shed new light on the early prognosis of cancer therapy for CRC in the future.
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, National Cheng-Kung University, Tainan 70101, Taiwan.
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Department of Pathology, National Cheng-Kung University Hospital, Tainan 70403, Taiwan.
authors.forename: Chung-Ta
authors.initials: CT
authors.lastname: Lee
authors.affiliation: Department of Surgery, National Cheng-Kung University Hospital, Tainan 70403, Taiwan.
authors.forename: Jenq-Chang
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Pathology, Kuo General Hospital, Tainan 70054, Taiwan.
authors.forename: Yao-Wen
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng-Kung University, Tainan 70101, Taiwan.
authors.forename: Ying-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, National Cheng-Kung University, Tainan 70101, Taiwan.|Department of Biotechnology and Bioindustry Sciences, National Cheng-Kung University, Tainan 70101, Taiwan.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Tseng
authors.affiliation: Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan 70403, Taiwan.
authors.forename: Jui-Wen
authors.initials: JW
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan 70403, Taiwan.
authors.forename: Bor-Shyang
authors.initials: BS
authors.lastname: Sheu
authors.affiliation: Department of Surgery, National Cheng-Kung University Hospital, Tainan 70403, Taiwan.
authors.forename: Bo-Wen
authors.initials: BW
authors.lastname: Lin
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, National Cheng-Kung University, Tainan 70101, Taiwan.|Department of Biotechnology and Bioindustry Sciences, National Cheng-Kung University, Tainan 70101, Taiwan.|Center for Infectious Disease and Signal Transduction Research, College of Medicine, National Cheng-Kung University, Tainan 70101, Taiwan.|Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Liang-Yi
authors.initials: LY
authors.lastname: Hung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D064096:Aurora Kinase A / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003111:Colonic Polyps / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D019175:DNA Methylation; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009368:Neoplasm Transplantation
chemical_list: C545567:MIRN137 microRNA, human; D035683:MicroRNAs; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: Aurora-A; COX2; colorectal cancer; epigenetic regulation; miR-137