異源性核糖核蛋白Q1 (hnRNP Q1)是一種多功能核糖核酸結合蛋白，負責調節核糖核酸在細胞內的代謝過程。hnRNP Q1在大腸直腸癌中的大量表現已知與細胞增殖有關，然而機制尚不清楚。我們透過RNA免疫沉澱結合次世代定序方法，找到一群與細胞週期相關的基因可能受到hnRNP Q1調控，其中包括極光激脢-A (Aurora-A)。Aurora-A為一致癌基因，參與細胞週期的調控，並與癌細胞內多條訊息傳遞路徑相關。利用生物素標定沉降法以及表面電漿共振儀，我們發現hnRNP Q1可經由本身蛋白上的核糖核酸結合區域2及3結合至Aurora-A的5端非轉譯區。當在大腸直腸癌細胞株內大量表現hnRNP Q1可以增加Aurora-A的蛋白表現但不影響mRNA。利用核糖蛋白S6免疫沉澱法、多核糖體分離及轉譯質體分析，我們確認hnRNP Q1可以促進Aurora-A mRNA的轉譯經由5端依賴性及非依賴性的調控機制。大量表現hnRNP Q1無論在體外或小鼠皮下皆能促進大腸直腸癌細胞的生長，另外在大腸直腸癌組織內我們發現hnRNP Q1的表現與Aurora-A呈正相關性。總結以上，我們首度發現hnRNP Q1是Aurora-A的轉譯調控因子，其在大腸直腸癌細胞的大量表現可能與細胞增殖及引發癌變有關。

HnRNP Q1 is a multifunctional RNA-binding protein involved in RNA metabolic regulation. Overexpressed hnRNP Q1 associated with tumor proliferation in colorectal cancer, however, the molecular mechanism is still unclear. To identify the targets of hnRNP Q1, we performed RNA-IP following high-throughput sequencing. A group of cell cycle-related genes, including Aurora-A kinase, which might be targeted by hnRNP Q1 were identified. Aurora-A is an oncogenic protein involved in regulating cell cycle progression and also in activating multiple signaling pathways in cancer cells. By biotin pull down and biacore assays, we found that hnRNP Q1 can directly bind to the 5’-untranslated region (UTR) of Aurora-A mRNA through the RNA-binding domains 2 and 3 (RBD23). Overexpressed hnRNP Q1 increases Aurora-A protein expression, but not mRNA level. Ribosomal protein S6-IP, polysome fractionation and translatome analysis further confirmed that hnRNP Q1 can enhance the translational efficiency of Aurora-A mRNA. Interestingly, Aurora-A mRNA can be translationally regulated by either cap-dependent or IRES-mediated mechanism. Overexpressed hnRNP Q1 can promote tumor cell proliferation in vitro and tumorigenesis in xenograft animal model, and is positively correlated with Aurora-A in colorectal cancer tissues. Taken together, our data reveal that hnRNP Q1 is a novel trans-acting factor that binds to Aurora-A 5’-UTR to up-regulate its translation, which may increase the cell proliferation and contribute to the tumorigenesis of colorectal cancer.

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