Abstract 2882: HnRNP Q1, a novel translational regulator for Aurora-A protein synthesis in colorectal cancer

Abstract

Abstract HnRNP Q1 is a multifunctional RNA-binding protein and has an abundant expression level compared with hnRNP Q member. In colorectal cancer, hnRNP Q has been reported to associate with cell proliferation, but the underlying mechanism is still unclear. By RNA-immunoprecipitation assay following next-generation sequencing (NGS), a group of cell cycle-related genes was identified to be targeted by hnRNP Q1, including Aurora-A kinase. 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 defects and aneuploidy, which might lead to genomic instability and tumorigenesis. Our previous work has demonstrated that Aurora-A can be translational up-regulated in colorectal cancer. In order to investigate the role of hnRNP Q1 in Aurora-A expression, GFP-hnNRP Q1 was overexpressed in colorectal cancer cells. We found that Aurora-A protein, but not the mRNA level, was up-regulated in those GFP-hnRNP Q1-overexpressing cells. By biotin pull down and Biacore analysis, we revealed that hnRNP Q1 binds to the 5’-UTRs of Aurora-A mRNA directly, and their interacting domain was mapped. Importantly, we found that hnRNP Q1 can enhance Aurora-A protein synthesis through IRES-mediated translational regulation in a cell cycle-regulated manner by ribosomal protein S6 immunoprecipitation, polysome fractionation and bicistronic reporter assay. CCK-8 assay, colony formation and in vivo xenograft assay all suggested that overexpression of hnRNP Q1 can promote cell proliferation and tumorigenesis of colorectal cancer cells. In addition, the expression level of hnRNP Q1 is positively correlated with Aurora-A in clinical colorectal cancer tissues. Taken together, our data indicate that hnRNP Q1 is a novel trans-acting factor that binds to Aurora-A 5’-UTRs and regulates its translation, which may increase cell proliferation and contribute to the tumorigenesis of colorectal cancer. Citation Format: Chien-Hsien Lai, Liang-Yi Hung. HnRNP Q1, a novel translational regulator for Aurora-A protein synthesis in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2882.