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Translational upregulation of Aurora-A by hnRNP Q1 contributes to cell proliferation and tumorigenesis in colorectal cancer

By using RNA-immunoprecipitation assay following next-generation sequencing, a group of cell cycle-related genes targeted by hnRNP Q1 were identified, including Aurora-A kinase. Overexpressed hnRNP Q1 can upregulate Aurora-A protein, but not alter the mRNA level, through enhancing the translational...

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Detalles Bibliográficos
Autores principales: Lai, Chien-Hsien, Huang, Yu-Chuan, Lee, Jenq-Chang, Tseng, Joseph Ta-Chien, Chang, Kung-Chao, Chen, Yen-Ju, Ding, Nai-Jhu, Huang, Pao-Hsuan, Chang, Wen-Chang, Lin, Bo-Wen, Chen, Ruo-Yu, Wang, Yu-Chu, Lai, Yi-Chien, Hung, Liang-Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386382/
https://www.ncbi.nlm.nih.gov/pubmed/28079881
http://dx.doi.org/10.1038/cddis.2016.479
Descripción
Sumario:By using RNA-immunoprecipitation assay following next-generation sequencing, a group of cell cycle-related genes targeted by hnRNP Q1 were identified, including Aurora-A kinase. Overexpressed hnRNP Q1 can upregulate Aurora-A protein, but not alter the mRNA level, through enhancing the translational efficiency of Aurora-A mRNA, either in a cap-dependent or -independent manner, by interacting with the 5′-UTR of Aurora-A mRNA through its RNA-binding domains (RBDs) 2 and 3. By ribosomal profiling assay further confirmed the translational regulation of Aurora-A mRNA by hnRNP Q1. Overexpression of hnRNP Q1 promotes cell proliferation and tumor growth. HnRNP Q1/ΔRBD23-truncated mutant, which loses the binding ability and translational regulation of Aurora-A mRNA, has no effect on promoting tumor growth. The expression level of hnRNP Q1 is positively correlated with Aurora-A in colorectal cancer. Taken together, our data indicate that hnRNP Q1 is a novel trans-acting factor that binds to Aurora-A mRNA 5′-UTRs and regulates its translation, which increases cell proliferation and contributes to tumorigenesis in colorectal cancer.