VRK1 can be a novel therapeutic target in small cell neuroendocrine carcinoma of the uterine cervix

Small cell neuroendocrine carcinoma of the uterine cervix (SCNEC) is a rare and highly aggressive cancer. In this study, we aimed to investigate the potential of vaccinia-related kinase 1 (VRK1) as a therapeutic target for SCNEC and to elucidate its functional mechanisms. VRK1 expression was found to be higher in SCNEC than in other histological types of cervical cancer. In both 3D cell culture and subcutaneous mouse models, shRNA-mediated VRK1 knockdown (shVRK1) exhibited significant antitumor effects. Gene Set Enrichment Analysis of RNA-seq data from the subcutaneous mouse models indicated that the effects of VRK1 are related to responses to external stimuli and mitochondrial pathways. In vitro, mitochondrial membrane potential was significantly decreased under hydrogen peroxide stimulation in shVRK1 cells compared to controls, suggesting that VRK1 knockdown induces mitochondrial dysfunction under external stimuli. In summary, VRK1 may be a promising therapeutic target for SCNEC, particularly through its role in mitochondrial responses to external stimuli. Overall design: To investigate the function of VRK1, we established HCSC-1 and TC-YIK cells with VRK1 knockdown via shRNA (shVRK1) and corresponding control cells (shCont). These cells were transplanted subcutaneously into mice, and the resulting tumors were excised. Gene Set Enrichment Analysis was then performed on RNA-seq data obtained from these tumors.