Correction: Enhancer of Zeste Homolog 2 Induces Pulmonary Artery Smooth Muscle Cell Proliferation

Aljubran, Salman; Cox, Ruan; Parthasarathy, Prasanna Tamarapu; Ramanathan, Gurukumar Kollongod; Rajanbabu, Venugopal; Huynh, Bao; Mohapatra, Shyam S.; Lockey, Richard F.; Kolliputi, Narasaiah

doi:10.1371/annotation/8580b50a-1556-4c86-aeb6-a88af839297a

Cited by 7 publications

(4 citation statements)

References 29 publications

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“…Several cancer cell lines proliferate when EZH2 is overexpressed, whereas tumor growth is inhibited by EZH2 suppression. Surprisingly, EZH2 has been demonstrated to prevent the progression of PAH by preventing hPASMC migration and proliferation [21,99]. The potential benefits of EZH2 inhibitors as cancer therapies are highlighted by the fact that inhibiting EZH2 decreases the proliferation of numerous cancer cell lines [100].…”

Section: Comparison Of Sin3a's Effects On Cancer and Its Implications...mentioning

confidence: 99%

Switch-Independent 3A: An Epigenetic Regulator in Cancer with New Implications for Pulmonary Arterial Hypertension

Jankowski,

Jagana,

Bisserier

et al. 2023

Biomedicines

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Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA, play a crucial role in the regulation of gene expression and are pivotal in biological processes like apoptosis, cell proliferation, and differentiation. SIN3a serves as a scaffold protein and facilitates interactions with transcriptional epigenetic partners and specific DNA-binding transcription factors to modulate gene expression by adding or removing epigenetic marks. However, the activation or repression of gene expression depends on the factors that interact with SIN3a, as it can recruit both transcriptional activators and repressors. The role of SIN3a has been extensively investigated in the context of cancer, including melanoma, lung, and breast cancer. Our group is interested in defining the roles of SIN3a and its partners in pulmonary vascular disease. Pulmonary arterial hypertension (PAH) is a multifactorial disease often described as a cancer-like disease and characterized by disrupted cellular metabolism, sustained vascular cell proliferation, and resistance to apoptosis. Molecularly, PAH shares many common signaling pathways with cancer cells, offering the opportunity to further consider therapeutic strategies used for cancer. As a result, many signaling pathways observed in cancer were studied in PAH and have encouraged new research studying SIN3a’s role in PAH due to its impact on cancer growth. This comparison offers new therapeutic options. In this review, we delineate the SIN3a-associated epigenetic mechanisms in cancer and PAH cells and highlight their impact on cell survival and proliferation. Furthermore, we explore in detail the role of SIN3a in cancer to provide new insights into its emerging role in PAH pathogenesis.

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Section: Comparison Of Sin3a's Effects On Cancer and Its Implications...mentioning

confidence: 99%

Switch-Independent 3A: An Epigenetic Regulator in Cancer with New Implications for Pulmonary Arterial Hypertension

Jankowski,

Jagana,

Bisserier

et al. 2023

Biomedicines

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“…Accordingly, inhibition of G9a by its inhibitor BIX-01294 decreased the migration, proliferation, and contractility of fetal PASMCs in relation to a significantly increased global methylation level in the fetal PASMCs [ 106 ]. The expression level of the enhancer of zeste homolog 2 (EZH2) is increased in PASMCs isolated from PAH animals, leading to enhanced hypertrophy, right-ventricle systolic pressure, and PAH development [ 107 ]. Similarly, the upregulation of EZH2 in human PASMCs increases migration and proliferation, as well as reduces apoptosis [ 107 ].…”

Section: Epigenetic Mechanisms Of Pathogenesis In Pahmentioning

confidence: 99%

“…The expression level of the enhancer of zeste homolog 2 (EZH2) is increased in PASMCs isolated from PAH animals, leading to enhanced hypertrophy, right-ventricle systolic pressure, and PAH development [ 107 ]. Similarly, the upregulation of EZH2 in human PASMCs increases migration and proliferation, as well as reduces apoptosis [ 107 ]. Shi et al identified that pharmacologic suppression of EZH2 with EPZ005687 improves transverse aortic constriction (TAC)-induced PAH by blocking ROS generation in the pulmonary system [ 108 ].…”

Section: Epigenetic Mechanisms Of Pathogenesis In Pahmentioning

confidence: 99%

Epigenetic Mechanisms as Emerging Therapeutic Targets and Microfluidic Chips Application in Pulmonary Arterial Hypertension

Hossen

Nguyen

et al. 2022

Biomedicines

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Pulmonary arterial hypertension (PAH) is a disease that progress over time and is defined as an increase in pulmonary arterial pressure and pulmonary vascular resistance that frequently leads to right-ventricular (RV) failure and death. Epigenetic modifications comprising DNA methylation, histone remodeling, and noncoding RNAs (ncRNAs) have been established to govern chromatin structure and transcriptional responses in various cell types during disease development. However, dysregulation of these epigenetic mechanisms has not yet been explored in detail in the pathology of pulmonary arterial hypertension and its progression with vascular remodeling and right-heart failure (RHF). Targeting epigenetic regulators including histone methylation, acetylation, or miRNAs offers many possible candidates for drug discovery and will no doubt be a tempting area to explore for PAH therapies. This review focuses on studies in epigenetic mechanisms including the writers, the readers, and the erasers of epigenetic marks and targeting epigenetic regulators or modifiers for treatment of PAH and its complications described as RHF. Data analyses from experimental cell models and animal induced PAH models have demonstrated that significant changes in the expression levels of multiple epigenetics modifiers such as HDMs, HDACs, sirtuins (Sirt1 and Sirt3), and BRD4 correlate strongly with proliferation, apoptosis, inflammation, and fibrosis linked to the pathological vascular remodeling during PAH development. The reversible characteristics of protein methylation and acetylation can be applied for exploring small-molecule modulators such as valproic acid (HDAC inhibitor) or resveratrol (Sirt1 activator) in different preclinical models for treatment of diseases including PAH and RHF. This review also presents to the readers the application of microfluidic devices to study sex differences in PAH pathophysiology, as well as for epigenetic analysis.

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“…Also, a reduction of the mitochondria-localized deacetylase sirtuin 3 gene ( SIRT3 ) expression suppresses mitochondrial function, inhibits apoptosis, and activates several pulmonary hypertension-related transcription factors [124]. Besides, increased expression of a histone methyltransferase, the enhancer of zeste homologue 2, is found in proliferating PASMCs and associated with the progression of PH [125].…”

Section: The Epigenetics Of Ph-lhdmentioning

confidence: 99%

The Biological Bases of Group 2 Pulmonary Hypertension

Fernández

Yotti

González‐Mansilla

et al. 2019

IJMS

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Pulmonary hypertension (PH) is a potentially fatal condition with a prevalence of around 1% in the world population and most commonly caused by left heart disease (PH-LHD). Usually, in PH-LHD, the increase of pulmonary pressure is only conditioned by the retrograde transmission of the left atrial pressure. However, in some cases, the long-term retrograde pressure overload may trigger complex and irreversible biomechanical and biological changes in the pulmonary vasculature. This latter clinical entity, designated as combined pre- and post-capillary PH, is associated with very poor outcomes. The underlying mechanisms of this progression are poorly understood, and most of the current knowledge comes from the field of Group 1-PAH. Treatment is also an unsolved issue in patients with PH-LHD. Targeting the molecular pathways that regulate pulmonary hemodynamics and vascular remodeling has provided excellent results in other forms of PH but has a neutral or detrimental result in patients with PH-LHD. Therefore, a deep and comprehensive biological characterization of PH-LHD is essential to improve the diagnostic and prognostic evaluation of patients and, eventually, identify new therapeutic targets. Ongoing research is aimed at identify candidate genes, variants, non-coding RNAs, and other biomarkers with potential diagnostic and therapeutic implications. In this review, we discuss the state-of-the-art cellular, molecular, genetic, and epigenetic mechanisms potentially involved in PH-LHD. Signaling and effective pathways are particularly emphasized, as well as the current knowledge on -omic biomarkers. Our final aim is to provide readers with the biological foundations on which to ground both clinical and pre-clinical research in the field of PH-LHD.

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Correction: Enhancer of Zeste Homolog 2 Induces Pulmonary Artery Smooth Muscle Cell Proliferation

Cited by 7 publications

References 29 publications

Switch-Independent 3A: An Epigenetic Regulator in Cancer with New Implications for Pulmonary Arterial Hypertension

Switch-Independent 3A: An Epigenetic Regulator in Cancer with New Implications for Pulmonary Arterial Hypertension

Epigenetic Mechanisms as Emerging Therapeutic Targets and Microfluidic Chips Application in Pulmonary Arterial Hypertension

The Biological Bases of Group 2 Pulmonary Hypertension

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