Studying the clinical significance and downstream regulatory mechanism of epigenetic silenced microRNA-137 in colorectal carcinogenesis

  • 黃 鈺琄

Student thesis: Doctoral Thesis

Abstract

MicroRNAs constitute a new class of gene expression regulators that express aberrantly in cancer MiR-137 acts as a tumor suppressor in many kinds of cancers including colorectal cancer (CRC) However the functional roles of miR-137 and its possibility to serve as a biomarker for clinical outcome in CRC remain largely unclear Our study indicated that miR-137 silences in human CRC tissues and colon polyps owing to the methylation of the miR-137 promoter region Several oncogenes involved in the carcinogenesis of CRC including Aurora-A PTGS2 CDK6 and CDC42 are the targets of miR-137 The expression pattern of miR-137 and Aurora-A or PTGS2 is negatively correlated in human CRC tissues and colon polyps Importantly the decreased expression level of miR-137 is significantly different in various types of polyps that maintain different potentials to lead to the development of CRC In a receiver operating characteristic (ROC) curve analysis loss of miR-137 expression as well as overexpressed Aurora-A or PTGS2 in colon polyps can serve as a biomarker to predict a predisposition for colorectal carcinogenesis Enforcing expression of miR-137 in CRC cells and in a xenograft animal model can result in the reduction of cell proliferation and tumor formation G2/M arrest and finally lead to apoptosis Additionally Azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CRC can be restored by Decitabine treatment Taken together our study suggests that epigenetic silencing of miR-137 in colon polyps can serve as a biomarker to predict a tendency towards 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 early prognosis or cancer therapy for CRC in the future
Date of Award2017 Jul 26
Original languageEnglish
SupervisorLiang-Yi Hung (Supervisor)

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