Molecular Alteration Analysis of BEND5 Gene and Its Clinical Significance in Colorectal cancer

• Main Authors: Yu-Fang Huang, 黃雨芳
• Other Authors: Ruo-Kai Lin
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/4k8zz8

碩士 === 臺北醫學大學 === 生藥學研究所 === 102 === Colorectal cancer (CRC) is the most frequently diagnosed cancer in Taiwan. Colorectal cancer occurrence rates have been increasing in recent years. It was the third leading cause of cancer death on 2011. DNA methylation is common abnormality in colorectal cancer (CRC). Aberrant promoter hypermethylation of TSG-associated CpG islands can lead to transcriptional silencing and result in tumorigenesis. DNA methylation is catalyzed by enzymes known as DNA methyltransferases. We applied Illumina human methylation 450K to identify loci hypermethylation in 26 primary CRCs relative to non-neoplastic colorectal tissue. A candidate tumor suppressor gene, BEND5 showed 82.35% (70 of 85) hypermethylation in colorectal tumors compared to matched normal colorectal tissues, especially in patients with metastasis in regional lymph nodes 95.2% (20/21) (p = 0.030). This CRC-associated hypermathylation events were evaluated by quantitative methylation specific real-time PCR (qMSP-PCR). Using real-time PCR found 71% (24 of 34) BEND5 mRNA expression was down-regulation in CRCs compared to matched normal colorectal tissues. Transient transfection of BEND5 and/or si-BEND5 found BEND5 could inhibit colon cancer cell proliferation. In addition, BEND5 was expressed in nucleus by detecting immunofluorescence when BEND5 was transfected into cell line. In conclusion, BEND5 alteration may play an important role in colorectal cancer. The predominana mechanisms of BEND5 inactivation were BEND5 promoter hypermathylation. The present study suggested that the alteration of BEND5 may be involved in tumor development. We thought BEND5 is a candidate tumor suppressor gene in colorectal cance.