Epigenetic silencing of miR-137 contributes to early colorectal carcinogenesis by impaired Aurora-A inhibition
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Yu-Chuan Huang1, Chung-Ta Lee5,*, Jenq-Chang Lee7,*, Yao-Wen Liu8, Ying-Jen Chen3, Joseph T. Tseng1,2, Jui-Wen Kang6, Bor-Shyang Sheu6, Bo-Wen Lin7, Liang-Yi Hung1,2,4,9
1Institute of Bioinformatics and Biosignal Transduction, National Cheng-Kung University, Tainan 70101, Taiwan
2Department of Biotechnology and Bioindustry Sciences, National Cheng-Kung University, Tainan 70101, Taiwan
3Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng-Kung University, Tainan 70101, Taiwan
4Center for Infectious Disease and Signal Transduction Research, College of Medicine, National Cheng-Kung University, Tainan 70101, Taiwan
5Department of Pathology, National Cheng-Kung University Hospital, Tainan 70403, Taiwan
6Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan 70403, Taiwan
7Department of Surgery, National Cheng-Kung University Hospital, Tainan 70403, Taiwan
8Department of Pathology, Kuo General Hospital, Tainan 70054, Taiwan
9Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
*These authors contributed equally to this work
Liang-Yi Hung, email: firstname.lastname@example.org
Bo-Wen Lin, email: email@example.com
Keywords: miR-137, Aurora-A, COX2, colorectal cancer, epigenetic regulation
Received: May 14, 2016 Accepted: October 12, 2016 Published: October 18, 2016
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.
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