| 摘要: | 無論在全球或是台灣大腸直腸癌的發生率以及死亡率，都排名在前三名，年齡、性別以及基因，都是大腸直腸癌發生的重要危險因子。而Wnt訊息路徑活化是大腸直腸癌發生的主要原因，在歐美國家中APC突變率達到80%以上，但在本實驗室過去的研究中，台灣的大腸直腸癌患者其APC突變率只有約為40%左右，因此本研究想瞭解是否存在其他的致病機轉，如microRNA，參與Wnt訊息路徑調控而促使台灣大腸直腸癌的發生。
本研究選定四個 microRNA 分別是miR-21、miR-200a、miR-135a及miR-135b，這些microRNA分別有文獻指出可以分別調控Wnt訊息路徑中各個重要的調節因子，如E-cadherin、Wnt 1及APC等。本研究以qRT-PCT分析156位大腸直腸癌患者之腫瘤組織中各個 microRNA的表現情形及其與臨床因子的相關性，結果發現miR-21、miR-200a及miR-135a與臨床因子無關，但miR-135b則與性別、腫瘤期別、以及是否有淋巴結轉移呈現統計上的正相關。
進一步分析發現miR-135b與Wnt、β-catenin及APC基因表現並無統計上的相關性，但miR-135b之上游之STAT3與β-catenin以及C-Myc基因表現均呈現有意義之正相關，因此推測 STAT3可能經由β-catenin之轉錄調控而影響miR-135b的表現參與台灣大腸直腸癌致病過程。
Colorectal cancer (CRC) is one of the leading causes of cancer death in both the Western world and Taiwan. Age, gender, and genes are important risk factors for colorectal cancer. Activation of Wnt signaling pathway is an important step involved in the pathogenesis of colorectal cancer. Approximately 70–80% of sporadic colorectal carcinomas have somatic mutations that inactivate APC. But, only 30% CRC patients in Taiwan have APC gene mutation that was significantly lower than the other countries. Thus, the other mechanism involved in APC gene inactivation may contributed to CRC progression in Taiwan. Here, we focus on the Wnt signaling associate microRNAs.
We selected four wnt signaling associated microRNAs, including miR-21, miR-200a, miR-135a and miR-135b. A total of 156 colorectal cancer patients were enrolled in this study. The expression of miR-21, miR-200a, miR-135a, miR-135b and wnt signaling association genes were analyzed by quantitative RT-PCR. The results showed that expression of miR-21, miR-200a and miR-135a were not associated with clinical parameters. Expression of miR-135b were positive correlated with gender, tumor stage, and lymph node metastasis. No any significantly correlation were found between miR-135b, Wnt,β-catenin and APC. But we can observed the positive correlation between STAT3, the upstream gene of miR-135b, β-catenin and C-Myc. Thus, we hypothesized that upregulation of miR-135b may throughβ-catenin mediated STAT3 activation |
