Targeting of CDK1 and PRMT5 as a potential therapeutic combination for non-small cell lung cancer

Objectives: The potential treatment option of targeting protein arginine methyltransferase 5 (PRMT5) has been explored, but further investigation is required to assess the efficacy of combination therapy in non-small cell lung cancer (NSCLC). In this study, bioinformatics and online databases were utilized to select the combined therapeutic targets. Methods: The potential kinases associated with PRMT5-related genes in NSCLC were analyzed using The Cancer Genome Atlas (TCGA) database and X2K Appyter (Expression2Kinases) database. In vitro evaluations were conducted to assess the synergistic effects between PRMT5 and cyclin-dependent kinase 1 (CDK1) in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) cell lines. Results: In our study, CDK1 was primarily the kinase associated with PRMT5-related genes in NSCLC. We observed a significant upregulation of PRMT5 and CDK1 expression in NSCLC tissues. Methylthioadenosine phosphorylase (MTAP)-null NSCLC cell lines demonstrated sensitivity to monotherapy with PRMT5i. A considerable synergistic effect was observed in MTAP-null cells when combining PRMT5i with CDK1i, resulting in the inhibition of cell growth and migration. Conclusion: Our research provides evidence supporting the synergistic anti-tumor effects of targeting PRMT5 and CDK1 in MTAP-deficient NSCLC.