揭示CEP55基因在大腸直腸癌轉移中所扮演的角色;Clarifying role of CEP55 in colorectal cancer metastasis

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题名:	揭示CEP55基因在大腸直腸癌轉移中所扮演的角色;Clarifying role of CEP55 in colorectal cancer metastasis
作者:	林揚芷;Lin,Yang-Chih
贡献者:	系統生物與生物資訊研究所
关键词:	大腸直腸癌;轉移;CEP55;高通量定序技術;Colorectal cancer;metastasis;CEP55;high-throughput mRNA sequencing
日期:	2015-07-14
上传时间:	2015-09-23 11:28:01 (UTC+8)
出版者:	國立中央大學
摘要:	大腸直腸癌好發率高居世界第三，且轉移性大腸直腸癌會使治療更加困難。本研究討論CEP55在大腸直腸癌扮演的角色，以釐清轉移性大腸直腸癌的機制。CEP55是一個轉錄中心體蛋白，在細胞增生上扮演重要角色，且已被發現在肝癌、肺癌、頭頸癌和鼻咽癌中過度表現。此研究包含三個部分，第一個部分是利用四個獨立公開的數據組來比較大腸直腸癌患者與健康族群的CEP55的表現量。第二部分是利用免疫組織染色程度來評估110例大腸直腸癌的CEP55表現量和淋巴結擴散程度的相關性。第三部分，藉由質體轉染及小分子干擾核糖核酸來改變HCT116細胞中CEP55的表現程度，再利用高通量信息RNA定序來得到CEP55的完整調控資訊。結果顯示，CEP55在大腸直腸癌的表現量升高。且CEP55的表現量與淋巴結擴散程度呈正相關性。最後結果顯示CEP55能促進細胞的爬行，並利用高通量定序技術，揭示跟CEP55共同調控的基因、功能及路徑。以上的整體結果能幫助深入了解轉移性大腸直腸癌的分子機制，也示意CEP55可能做為治療轉移性大腸直腸癌的標靶。;Colorectal cancer (CRC) has the third highest incidence rate among all cancers worldwide and becomes radically more difficult to treat when it is metastatic. Here, to provide insight into the mechanisms underlying CRC metastasis, we describe the role in CRC metastasis of CEP55, which is the encoding gene of a centrosomal protein essential to proliferation and has been reported to be overexpressed in hepatocellular carcinoma, lung cancer, head and neck cancer and nasopharyngeal carcinomas. The study comprises three steps. The first step was to measure the relative expression levels of CEP55 in CRC patients compared with healthy controls, using four independent public datasets. The second step was to assess correlation between metastasis and CEP55 expression level, using 110 staged CRCs and their Immunohistochemistry-based grades. The third step was to artificially alter CEP55 expression levels in HCT116 cells, using plasmid-implanted CEP55 clones and siRNA knockdowns, and to apply high-throughput mRNA sequencing to holistically profile the resultant co-regulation information. The results show elevated CEP55 levels in CRCs over controls. And the results reveal positive correlation between CEP55 level and spreading status to lymph nodes. CEP55 promotes cell migration and delineates the involved genes, functions and pathways in CEP55 co-regulation. The results overall pave the way for deeper understandings of the underlying molecular mechanisms and suggest CEP55 as a therapeutic target for CRC metastasis.
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