Related Experiment Video

Updated: Jul 1, 2025

Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
08:01

Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines

Published on: April 21, 2022

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POLD1 Is Required for Cell Cycle Progression by Overcoming DNA Damage in Malignant Pleural Mesothelioma

Daiki Shimizu1, Miku Ishibashi1, Tadaaki Yamada2

  • 1Laboratory of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.

Cancer Genomics & Proteomics
|February 29, 2024
PubMed
Abstract

Insights

High DNA polymerase delta 1 (POLD1) expression correlates with poor survival in malignant pleural mesothelioma (MPM) patients. Targeting POLD1 induces cell cycle arrest and apoptosis, suggesting POLD1 as a potential therapeutic target for MPM.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Malignant pleural mesothelioma (MPM) has a poor prognosis due to limited therapeutic options.
  • Asbestos exposure-induced DNA damage is linked to MPM development, with frequent mutations in DNA damage repair (DDR) genes.
  • Identifying novel therapeutic targets in MPM is crucial for improving patient outcomes.

Purpose of the Study:

  • To identify novel therapeutic targets for MPM by analyzing DDR pathways.
  • To investigate the correlation between DDR-related gene expression and overall survival (OS) in MPM patients.
  • To evaluate the anti-tumor effects of targeting specific DDR genes in MPM cell lines.

Main Methods:

  • Utilized The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases for gene expression analysis.
  • Correlated mRNA expression levels of DDR-related genes with OS in TCGA-MESO datasets.
  • Tested the anti-tumor effects of small interfering RNAs (siRNA) against identified DDR genes in MPM cell lines.

Main Results:

  • Elevated mRNA levels of DNA polymerase delta 1, catalytic subunit (POLD1) were significantly associated with reduced OS in MPM patients (p<0.001).
  • siRNA targeting POLD1 (siPOLD1) induced G1/S cell cycle arrest in MPM cell lines.
  • siPOLD1 treatment led to apoptosis and DNA damage accumulation in MPM cells.

Conclusions:

  • POLD1 is essential for DNA damage repair and cell cycle progression at the G1/S checkpoint in MPM cells.
  • POLD1 plays a critical role in MPM cell survival and proliferation.
  • POLD1 represents a promising novel therapeutic target for malignant pleural mesothelioma.
Keywords:
DNA damageDNA polymerase δMalignant pleural mesotheliomaPOLD1The Cancer Genome Atlascell cycle

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