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Metabolic pathways, genomic alterations, and post-translational modifications in pulmonary hypertension and cancer as therapeutic targets and biomarkers. | LitMetric

Metabolic pathways, genomic alterations, and post-translational modifications in pulmonary hypertension and cancer as therapeutic targets and biomarkers.

Front Pharmacol

Department of Cardiology, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China.

Published: November 2024

AI Article Synopsis

  • Pulmonary hypertension (PH) can cause serious heart issues, and this study investigates how specific metabolites and nutrients, like DHA and EPA, might help alleviate related oxidative stress and inflammation.
  • The research analyzed data from a large population to identify 57 metabolites connected to PH and tested the effects of DHA and EPA on inflammatory responses in macrophages and various cancer cell lines.
  • Results showed that DHA and EPA effectively reduced harmful reactive oxygen species (ROS) and cancer cell growth, highlighting their potential as therapeutic options for better managing PH and related cancer conditions.

Article Abstract

Background: Pulmonary hypertension (PH) can lead to right ventricular hypertrophy, significantly increasing mortality rates. This study aims to clarify PH-specific metabolites and their impact on genomic and post-translational modifications (PTMs) in cancer, evaluating DHA and EPA's therapeutic potential to mitigate oxidative stress and inflammation.

Methods: Data from 289,365 individuals were analyzed using Mendelian randomization to examine 1,400 metabolites' causal roles in PH. Anti-inflammatory and antioxidative effects of DHA and EPA were tested in RAW 264.7 macrophages and cancer cell lines (A549, HCT116, HepG2, LNCaP). Genomic features like CNVs, DNA methylation, tumor mutation burden (TMB), and PTMs were analyzed. DHA and EPA's effects on ROS production and cancer cell proliferation were assessed.

Results: We identified 57 metabolites associated with PH risk and examined key tumor-related pathways through promoter methylation analysis. DHA and EPA significantly reduced ROS levels and inflammatory markers in macrophages, inhibited the proliferation of various cancer cell lines, and decreased nuclear translocation of SUMOylated proteins during oxidative stress and inflammatory responses. These findings suggest a potential anticancer role through the modulation of stress-related nuclear signaling, as well as a regulatory function on cellular PTMs.

Conclusion: This study elucidates metabolic and PTM changes in PH and cancer, indicating DHA and EPA's role in reducing oxidative stress and inflammation. These findings support targeting these pathways for early biomarkers and therapies, potentially improving disease management and patient outcomes.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614602PMC
http://dx.doi.org/10.3389/fphar.2024.1490892DOI Listing

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