Publication: Targeting of CDK1 and PRMT5 as a potential therapeutic combination for non-small cell lung cancer
Authors
Chunwei Xu ; Yonghua Min ; Youcai Zhu ; Xiaofeng Li ; Zhanqiang Zhai
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Publisher
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Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-25-030
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info:eu-repo/semantics/article
Description
Abstract
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. Methylthio
adenosine 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.
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Citation
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