大腸直腸癌目前仍是全球最常見的惡性疾病，也是癌症致死率排名前三的主要癌症之一。儘管對於大腸直腸癌的發病機制已經投入了很多的努力與研究，但是該過程中所涉及的確切分子機制仍然有很大程度上是未知的。共激活因子相關的精氨酸甲基轉移酶-1（CARM1）是屬於蛋白質精氨酸甲基轉移酶的家族成員，主要的功能是催化位於蛋白質底物中的精氨酸（Arg）使其造成不對稱甲基化的結構。而根據先前已發表的文獻，CARM1可以涉及到多個重要的生物過程中，例如基因調控，細胞週期進展和DNA損傷反應。然而，CARM1的相關作用機制在癌症的中仍然還是不清楚的。因此，為了探究CARM1的表達是否有助於大腸直腸癌的發展，首先，我們收集了公共資料庫裡未被分析的大腸直腸癌病人的原始數據並且分析了CARM1的表達量，而我們的結果顯示，CARM1的表達量在大腸直腸癌中是增加的情形並且同時也發現高表達CARM1的病人有較低存活率。而在我們自己收取的大腸直腸癌病人樣本中也看到相似的結果。接著，為了證明CARM1的表現量是否會影響大腸直腸癌細胞的功能，我們通過小分子干擾核糖核酸（siRNA）在大腸直腸癌細胞系中降低了CARM1表達。從細胞增生以及細胞爬行的實驗結果中證實了，當CARM1的表達量被抑制的時候，確實會降低細胞增生以及爬行的能力。而為了進一步去研究造成CARM1在大腸直腸癌中高度表達的機制，我們利用生物資訊分析的方法，鑑定了位於CARM1啟動子區域中具有早期生長反應蛋白（EGR-1）的結合位點。由於在過去實驗室的發表中已證實了EGR-1的表達受到了雙特異性磷酸酶2（DUSP2）的負調控影響，因此，我們假設當DUSP2不表達的時候，可能藉由通過EGR-1來引起CARM1在大腸直腸癌中過度表達的情形。為了測試這個想法，我們利用小分子干擾核糖核酸（siRNA）將DSUP2在大腸直腸癌細胞系中降低後發現，抑制DUSP2確實引起CARM1表達量的增加。在DUSP2條件性剔除小鼠的腸組織中也觀察到類似的結果。綜合以上的結果，我們發現在大腸直腸癌中DUSP2的缺失導致CARM1過表達，進而促進大腸直腸癌的病理過程的發展。

Colorectal cancer is a common malignant disease and the third leading cause of cancer death in the world. Although intensive efforts have been devoted to investigate the pathogenesis of colorectal cancer, the exact molecular mechanisms involved in the process remain largely unknown. Coactivator-associated arginine methyltransferase 1 (CARM1), a member of protein arginine methyltransferase family, catalyzes asymmetric methylation of the arginine (Arg) residues in protein substrates. According to the published literatures, CARM1 involves in multiple important biological processes, such us gene regulation, cell-cycle progression, and the DNA damage response. However, the mechanism of CARM1 action remains obscure in cancer. To characterize whether the expression of CARM1 contributes to the development of colorectal cancer, we first evaluated the level of CARM1 in the colorectal cancer specimens from the public datasets. Our data demonstrated that CARM1 expression was up regulated in colorectal cancer and negatively associated with poor survival. Similar results were also observed in our own colorectal cancer samples. Next, to demonstrate whether the CARM1 expression affects cellular function, CARM1 was knocked down by siRNA in colorectal cancer cell line and its cellular functions were evaluated. Cell proliferation and migration assays demonstrated that knockdown of CARM1 significantly repressed cell proliferative and migratory abilities. To further investigate the underlying mechanism causing CARM1 overexpression in colorectal cancer, we identified EGR-1 binding sites located in the CARM1 promoter region through bioinformatics analysis. Since our previous data demonstrated that EGR-1expression was negatively regulated by Dual Specificity Phosphatase 2 (DUSP2), we thus hypothesized that loss of DUSP2 may cause CARM1 overexpression via EGR-1-mediated gene transcription. To test the idea, DUSP2 was knocked down by siRNA in colorectal cancer cells. Knockdown of DUSP2 indeed caused an increase of CARM1 expression. Similar results were observed in the intestine tissues from DUSP2 conditional knockout mice and supported by the clinical specimen analysis. In summary, we have found that loss of DUSP2 results in CARM1 overexpression, which promotes pathological processes of colorectal cancer.

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