VRK1 promotes proliferation, migration, and invasion of gastric carcinoma cells by activating β-catenin

Vaccinia-related kinase 1 (VRK1) is a member of the VRK subfamily belonging to the casein kinase superfamily, and it regulates the proliferation and survival of cells both in normal and malignant tissues. A variety of transcription factors including c-Jun can also be specifically phosphorylated and stimulated by VRK1. However, the regulatory mechanism of VRK1 in gastric carcinoma (GC) remains unclear. This research aimed to determine the function of VRK1 during tumor progression in GC. The mRNA and protein expression of the VRK1 and other genes were evaluated in GC cell lines using real-time RT-PCR and western blotting. Cell proliferation was analyzed using the cell count kit-8 (CCK-8) assay, and cell migration and invasion were monitored by the Transwell assay. The downregulated genes in shVRK1 cells compared with shCtrl were assessed using RNA-seq. The interactions of VRK1 with beta-catenin or c-Jun were detected by co-IP. We found that VRK1 was overexpressed in gastric cancer cells, conversely, knockdown of VRK1 inhibits GC cells' proliferation, migration, and invasion. Moreover, VRK1 might regulate the expression of beta-catenin (CTNNB1) at the transcriptional level by phosphorylating c-Jun, the transcriptional factor of beta-catenin. VRK1 changes the subcellular location and decreases the nuclear aggregation of c-Jun by phosphorylating the Ser243 site. To conclude, VRK1 can affect migration and invasion by regulating the expression of beta-catenin at the transcriptional level in GC cells.

Automated summary

The study demonstrates that overexpression of VRK1 in gastric cancer cells promotes cell proliferation, migration, and invasion, and possibly regulates the transcriptional level of beta-catenin by phosphorylating c-Jun. Knockdown of VRK1 inhibits these processes, suggesting a potential role for VRK1 in tumor progression in gastric carcinoma.