EGF translationally up-regulates the Aurora-A mRNA via hnRNP Q1-mediated mechanism in colorectal cancer

Abstract

Aurora-A which is a serine/threonine kinase involved in regulating cell cycle progression is frequently amplified and overexpressed in variety of cancers Deregulation of Aurora-A has major roles in tumorigenesis Heterogeneous nuclear ribonucleoprotein (hnRNP) Q1 an RNA binding protein has been implicated in many post-transcriptional regulatory processes including mRNA splicing RNA metabolism and translation Using an RNA-immunoprecipitation (RIP)-seq analysis a group of cell cycle-related genes targeted by hnRNP Q1 were identified including Aurora-A kinase Altering the hnRNP Q1 level influences the expression of the Aurora-A protein but not its mRNA Stimulation with epidermal growth factor (EGF) is found to enhance both binding between hnRNP Q1 and the Aurora-A mRNA as well as the efficacy of the hnRNP Q1-induced translation of the Aurora-A mRNA The EGF/hnRNP Q1-induced translation of Aurora-A mRNA is mediated by the mTOR and ERK pathways We also show that hnRNP Q1 up-regulates the translation of a group of spindle assembly checkpoint (SAC) genes hnRNP Q1 overexpression is positively correlated with the levels of Aurora-A and these SAC genes in human colorectal cancer tissues Taken together our data indicate that hnRNP Q1 plays an important role in regulating a group of cell cycle-related genes expression hnRNP Q1 may therefore contribute to tumorigenesis by up-regulating the translation of these genes in colorectal cancer

Date of Award	2018 Jul 30
Original language	English
Supervisor	Liang-Yi Hung (Supervisor)