RNA-binding protein HNRNP A1 promotes lung cancer cell proliferation by targeting VRK1

Abstract

RNA-binding proteins (RBPs) are key players in post- transcriptional events. Dysregulation of gene expression is associated with a variety of diseases, including lung cancer. Vaccinia-related kinase 1 (VRK1) is a master regulator in lung adenocarcinoma and is considered a key molecule in the adaptive pathway, which mainly controls cell proliferation and survival. Previous studies have shown that VRK1 was significantly increased in various cancer cells, but detailed understanding for gene regulatory mechanisms of VRK1 is still unknown. Here we demonstrate that heterogeneous nuclear ribonucleoprotein (hnRNP) A1 enhances VRK1 mRNA translation. We found that 3′UTR of VRK1 mRNA increased protein amounts and hnRNP A1 binds to the 3′UTR of VRK1 mRNA. Furthermore, hnRNP A1 interacted with eukaryotic translation initiation factors and also directly associated with ribosomal proteins, resulting in translation of VRK1 mRNA in a 3′UTR-dependent manner. In conclusion, overexpression of hnRNP A1 promotes cell proliferation and invasion in lung cancer by regulating the level of VRK1 and have potential as therapeutic targets.