The EGF/hnRNP Q1 axis is involved in tumorigenesis via the regulation of cell cycle-related genes

摘要

Heterogeneous nuclear ribonucleoprotein (hnRNP) Q1, an RNA-binding protein, has been implicated in many post-transcriptional processes, including RNA metabolism and mRNA splicing and translation. However, the role of hnRNP Q1 in tumorigenesis remains unclear. We previously performed RNA immunoprecipitation (RIP)-seq analysis to identify hnRNP Q1-interacting mRNAs and found that hnRNP Q1 targets a group of genes that are involved in mitotic regulation, including Aurora-A. Here, we demonstrate that altering the hnRNP Q1 level influences the expression of the Aurora-A protein, but not its mRNA. Stimulation with epidermal growth factor (EGF) enhances both binding between hnRNP Q1 and Aurora-A mRNA as well as the efficacy of the hnRNP Q1-induced translation of Aurora-A mRNA. The EGF/hnRNP Q1-induced translation of Aurora-A mRNA is mediated by the mTOR and ERK pathways. In addition, we 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 the SAC genes in human colorectal cancer tissues. In summary, our data suggest that hnRNP Q1 plays an important role in regulating the expression of a group of cell cycle-related genes. Therefore, it may contribute to tumorigenesis by up-regulating the translation of these genes in colorectal cancer. Cancer: A regulator of cell cycle gene expression An RNA-binding protein contributes to cancer by boosting the protein-making potential of various genes involved in the cell cycle and cell division. Researchers in Taiwan led by Liang-Yi Hung from the National Cheng Kung University in Tainan, Taiwan, previously showed that a cancer-causing protein implicated in tumors of the colon and elsewhere gets induced by both an RNA-binding protein called hnRNP Q1 and a growth factor called EGF. Now, they have demonstrated that these two molecules work in concert to boost the efficiency by which the RNA encoding the cancer-causing protein gets translated into the protein. They also showed that hnRNP Q1 serves a similar RNA-modulating function for several genes involved in spindle checkpoint during cell division. Together, the findings point to hnRNP Q1 as a potential target for future anti-cancer drugs.