%0 Journal Article
%T Metabolic Reprogramming, Genomic Alterations, and Post-Translational Modifications in Pulmonary Hypertension and Cancer: Implications for Biomarkers and Therapeutic Targeting
%A Carlos Méndez
%A Javier Soto
%A Luis Calderón
%J Specialty Journal of Pharmacognosy, Phytochemistry, and Biotechnology
%@ 3062-441X
%D 2023
%V 3
%N 1
%R 10.51847/JAPK1fotYK
%P 164-182
%X Pulmonary hypertension (PH) often results in right ventricular hypertrophy, contributing to higher mortality. This study investigates PH-associated metabolites and their influence on genomic alterations and post-translational modifications (PTMs) in cancer, while assessing the therapeutic potential of DHA and EPA in reducing oxidative stress and inflammation. Using Mendelian randomization on a cohort of 289,365 individuals, we explored the causal involvement of 1,400 metabolites in pulmonary hypertension. The potential anti-inflammatory and antioxidant actions of DHA and EPA were investigated in RAW 264.7 macrophages and multiple cancer cell lines (A549, HCT116, HepG2, LNCaP). We further characterized genomic alterations—including CNVs, DNA methylation patterns, tumor mutation burden (TMB), and post-translational modifications (PTMs)—and evaluated how DHA and EPA influence reactive oxygen species production and the proliferation of cancer cells. A total of 57 metabolites were found to be associated with pulmonary hypertension risk, and critical tumor-related pathways were investigated via promoter methylation analysis. DHA and EPA markedly lowered ROS levels and inflammatory markers in macrophages, suppressed proliferation across multiple cancer cell lines, and reduced the nuclear translocation of SUMOylated proteins under oxidative and inflammatory conditions. These results indicate a potential anticancer effect through modulation of stress-responsive nuclear signaling and regulation of cellular post-translational modifications. This study highlights alterations in metabolism and post-translational modifications in pulmonary hypertension and cancer, demonstrating that DHA and EPA can mitigate oxidative stress and inflammatory responses. The results underscore the potential of targeting these pathways for developing early biomarkers and therapeutic strategies, offering promising avenues to enhance disease management and patient outcomes.”
%U https://galaxypub.co/article/metabolic-reprogramming-genomic-alterations-and-post-translational-modifications-in-pulmonary-hype-7041h1jbsjnu17b