Aurora-A 是一個serine/threonine蛋白激酶，參與在中心體成熟、有絲分裂期的進入、紡錘體組成和染色體分離。Aurora-A功能異常會造成中心體增殖，染色體無法正確分離到子細胞中，以致細胞染色體數目不正常，最後導致腫瘤形成。在許多的癌細胞中，Aurora-A 皆有過量表現的情形。我們過去的研究顯示，在EGF 的刺激之下，會透過Aurora-A mRNA特定的五端不轉譯區（5’UTR）來增加Aurora-A mRNA 轉譯的效率。同時，hnRNP Q1及hnRNP A2/B1這兩個RNA結合蛋白，則可能參與此Aurora-A mRNA轉譯的過程。在本研究中，我們先確認在人類臨床大腸直腸癌組織中，Aurora-A mRNA大多是具有此特定的五端不轉譯區的同源異構物。In vivo translation assay以及ribosomal protein S6 免疫沈澱實驗顯示，過量表現hnRNP Q1會增加Aurora-A mRNA轉譯的效率，而過量表現hnRNP A2/B1則會減少Aurora-A mRNA的轉譯效率。Biotin pull-down assay以及RNA 免疫沈澱的結果顯示，hnRNP Q1及hnRNP A2/B1分別會結合上Aurora-A mRNA五端不轉譯區不同的區域。利用BIAcore assay，我們亦確定了hnRNP Q1與Aurora-A五端不轉譯區結合的位置。以PCR分析臨床大腸直腸癌組織中Aurora-A及hnRNP Q1的表現，發現這兩者具有正相關。根據以上結果，我們認為hnRNP Q1及hnRNP A2/B1會透過與Aurora-A五端不轉譯區的結合，進而調控Aurora-A mRNA的轉譯。

Aurora-A is a serine/threonine kinase that involved in centrosome maturation, mitotic entry, spindle assembly and chromosome segregation. Dysregulation of Aurora-A results in centrosome amplification, cytokinesis failure, aneuploidy, and finally leads to tumor formation. It was reported that Aurora-A is overexpressed in a lot of cancers. Our previously studies indicated that EGF can translational up-regulate the expression of Aurora-A through a specific 5’-untranslated region (5’UTR). In addition, hnRNP Q1 and hnRNP A2/B1 may participate the translational regulation of Aurora-A mRNA. In this study, we investigate the role of hnRNP Q1 and hnRNP A2/B1 in translational regulating Aurora-A. The expression pattern of Aurora-A mRNA isoforms in human colorectal cancer was firstly confirmed by real-time PCR. In vivo translation assay and ribosomal protein S6-immunoprecipitation assay showed that hnRNP Q1 can increase the translation efficiency of Aurora-A, however hnRNP A2/B1 plays an opposite role. The biotin pull-down assay indicates hnRNP Q1 and hnRNP A2/B1 prefers to interact with different region of Aurora-A 5’UTR. BIAcore assay confirmed the Aurora-A 5’UTR-binding domain of hnRNP Q1. The expression of Aurora-A and hnRNP Q presents a positive correlation in clinical human colorectal cancer specimens by RT-PCR analysis. Taken together, our results suggest that hnNRP Q1 and hnRNP A2/B1 may translationally regulate Aurora-A mRNA through its 5’UTR.

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