Targeting phosphomevalonate kinase enhances radiosensitivity via ubiquitination of the replication protein A1 in lung cancer cells.

ABSTRACT: Radiotherapy (RT) plays an important role in localized lung cancer treatments. Although RT locally targets and controls malignant lesions, RT resistance prevents RT from being an effective treatment for lung cancer. In this study, we identified phosphomevalonate kinase (PMVK) as a novel radiosensitizing target and explored its underlying mechanism. We found that cell viability and survival fraction after RT were significantly decreased by PMVK knockdown in lung cancer cell lines. RT increased apoptosis, DNA damage, and G2/M phase arrest after PMVK knockdown. Also, after PMVK knockdown, radiosensitivity was increased by inhibiting the DNA repair pathway, homologous recombination, via downregulation of replication protein A1 (RPA1). RPA1 downregulation was induced through the ubiquitin-prote

SUBMITTER: Park SS 

PROVIDER: S-EPMC10475767 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature