Abstract HnRNP Q1 is a RNA-binding protein which belongs to hnRNP Q family and involves in pre-mRNA splicing, mRNA transport, translation and turnover. Data from Oncomine, which is a cancer microarray database, indicates that hnRNP Q1 is overexpressed in colorectal cancer. According the literatures, hnRNP Q1 can increase the translational efficiency through binding to the 5′-untranslated region (5′-UTR) of target genes. From RNA-IP assay following the next generation sequencing (NGS), we found that hnRNP Q1 regulates a group of cell cycle-related genes. Among them, Aurora-A is one of the targets of hnRNP Q1. Aurora-A is a cell-cycle dependent kinase involved in regulating centrosome duplication, maturation, and spindle assembly during mitosis. Abnormally elevated Aurora-A will cause mitotic defect and aneuploidy, which might lead to genomic instability and tumorigenesis. In addition, overexpression of hnRNP Q1 is positively correlated with overexpressed Aurora-A in clinical colorectal cancer tissues. Our previous report demonstrated that Aurora-A can be translational up-regulated in colorectal cancer. In this study, we demonstrated that hnRNP Q1 can bind to Aurora-A 5′-UTRs and also mapped the interacting domain between Aurora-A 5′UTR and hnRNP Q1 has been mapped by Biacore analysis, RNA-IP and biotin pull-down assay. Overexpressed hnRNP Q1 enhances the Aurora-A protein expression but doesn't alter its mRNA level. In contrast, repressed expression of hnRNP Q1 decreases the translation of Aurora-A. Importantly, we found that Aurora-A 5′UTR has IRES-dependent translational activity in a cell cycle regulated manner. Overexpression of hnRNP Q1 can up-regulate the IRES-dependent translation of Aurora-A during cell cycle progression, and promotes the cells proliferation. Taken together, our data indicate hnRNP Q1 is a novel trans-acting factor that binds on the Aurora-A 5′-UTRs and regulates it's translation, which may increase the cell proliferation and contribute to the tumorigenesis of colorectal cancer. Citation Format: Liang-Yi Hung. HnRNP Q1 contributes to tumorigenesis through the translational regulation of Aurora-A in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2127. doi:10.1158/1538-7445.AM2015-2127
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