VRK1 is a Novel Therapeutic Target for Small Cell Neuroendocrine Carcinoma of the Cervix

ABSTRACT: Small cell neuroendocrine carcinoma of the cervix (SCNEC) is classified as a high-grade neuroendocrine carcinoma of the cervix and has a worse prognosis than other major histological types of cervical cancer, such as squamous cell carcinoma and adenocarcinoma, due to the lack of effective treatments. Developing novel therapeutic targets based on its molecular characteristics is highly desirable; however, it has been limited due to the rarity of SCNEC and the resulting lack of research resources. Herein, we identified vaccinia-related kinase 1 (VRK1) as a potential therapeutic target for SCNEC. VRK1 was focused via our previous reported proteomic analysis of patient-derived organoids. Immunohistochemistry of patient samples revealed that VRK1 expression is consistently high in SCNEC, whereas its expression is variable in other cervical carcinomas. VRK1 knockdown significantly suppressed cell proliferation in three-dimensional cultures and xenograft tumor growth in vivo. Gene Set Enrichment Analysis of RNA-seq data obtained from mouse xenograft models indicated that VRK1 is associated with mitochondrial function. Subsequent in vitro experiments demonstrated that VRK1 knockdown suppressed SCNEC cell proliferation and simultaneously impaired mitochondrial function under the unique condition with oxidative stress. Finally, low VRK2 expression, proposed as a biomarker for the effectiveness of VRK1 knockdown, was consistently observed in SCNEC. These findings suggest that SCNEC is an optimal tumor group for targeting VRK1. VRK1 knockdown induced significant anti-tumor effects, highlighting its potential as a therapeutic target for SCNEC. Mechanistically, these effects appear to be mediated through mitochondrial dysfunction.

ORGANISM(S): Homo sapiens

PROVIDER: GSE285993 | GEO | 2026/01/31

REPOSITORIES: GEO