DNA Methylation Malleability and Dysregulation in Cancer Progression: Understanding the Role of PARP1

Srivastava, Rakesh K.; Lodhi, Niraj

doi:10.3390/biom12030417

Cited by 8 publications

(5 citation statements)

References 273 publications

(258 reference statements)

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“…It is worth noting that both mRNA and protein expression of PARP1 was stimulated by estrogen in hUSLFs. PARP1 is a ubiquitous multifunctional nuclear enzyme that catalyzes the transfer of ADP-ribose units from NAD + to specific target proteins and controls important physiological processes such as DNA methylation, DNA damage response, chromatin remodeling and gene expression ( Srivastava and Lodhi, 2022 ) ( Swindall et al, 2013 ) ( Hassa and Hottiger, 2008 ). Several studies have proved that ERα could be poly(ADP-ribosyl)ated by binding to PARP1 and promoting ERα-dependent gene transcription ( Zhang et al, 2013 ; Gadad et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

The protective effect of 17 β-estradiol on human uterosacral ligament fibroblasts from postmenopausal women with pelvic organ prolapse

Xie

Guo

et al. 2022

Front. Physiol.

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This study aims to explore the protective effects of 17 β-estradiol on the human uterosacral ligament fibroblasts (hUSLFs) under static or stretched conditions. The experiments were performed on hUSLFs derived from pelvic organ prolapse (POP) and non-POP patients. Fibroblasts were cultured after collagenase digestion and identified by morphological observation and immunocytochemical methods. 17 β-estradiol (10−10 M and 10−9 M) and mechanical stress induced by the FX-5000 T-cell stress loading system under a loading strain of 1/2 sin waveform uniaxial cyclic stress with a tensile strain of 20% and a frequency of 0.5 Hz were either or both applied on hUSLFs. Cell proliferation was measured by CCK8, and cell apoptosis and death were detected using Annexin V/7-AAD staining and flow cytometric analysis. We found that the fibroblasts growth rate of POP patients was significantly lower than controls. The cell apoptosis and death rate increased as the mechanical load intensifying. After 20% mechanical stretching for 24 h, the dead cell rate was higher in POP than control. Notably, 17 β-estradiol treatment reversed mechanical stress induced hUSLFs apoptosis and death in both POP and Control cells. The protein and mRNA levels of anti-apoptotic PARP1 (poly-ADP-ribose polymerase) and Bcl-2 were increased by estrogen treatment. Meanwhile, expression of estrogen receptor α, a target of Poly-ADP-Ribosylation of PARP1, was also enhanced by 17 β-estradiol under the mechanical load. In conclusion, estrogen application ameliorates the mechanical strain induced cell apoptosis and death in hUSLFs from POP patients. PARP1 might be involved in this protective process, providing novel insights into the mechanical biology of and possible therapies for POP.

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Section: Discussionmentioning

confidence: 99%

The protective effect of 17 β-estradiol on human uterosacral ligament fibroblasts from postmenopausal women with pelvic organ prolapse

Xie

Guo

et al. 2022

Front. Physiol.

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“…(4) Estrogen/poly-ADP-ribose polymerase 1 PARP1 reverses mechanical transduction damage. PARP1 is a multifunctional nuclear enzyme that catalyzes the transfer of ADP-ribose units from NAD+ to specific target proteins, which controls important physiological processes such as DNA damage and gene expression ( 64 ). PARP1 is an important member of the antiapoptotic protein family.…”

Section: Impact Of Biomechanical-biochemical Coupling On Fibroblast F...mentioning

confidence: 99%

Roles and mechanisms of biomechanical-biochemical coupling in pelvic organ prolapse

Wu,

Zhang,

et al. 2024

Front. Med.

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Pelvic organ prolapse (POP) is a significant contributor to hysterectomy among middle-aged and elderly women. However, there are challenges in terms of dedicated pharmaceutical solutions and targeted interventions for POP. The primary characteristics of POP include compromised mechanical properties of uterine ligaments and dysfunction within the vaginal support structure, often resulting from delivery-related injuries. Fibroblasts secrete extracellular matrix, which, along with the cytoskeleton, forms the structural foundation that ensures proper biomechanical function of the fascial system. This system is crucial for maintaining the anatomical position of each pelvic floor organ. By systematically exploring the roles and mechanisms of biomechanical-biochemical transformations in POP, we can understand the impact of forces on the injury and repair of these organs. A comprehensive analysis of the literature revealed that the extracellular matrix produced by fibroblasts, as well as their cytoskeleton, undergoes alterations in patient tissues and cellular models of POP. Additionally, various signaling pathways, including TGF-β1/Smad, Gpx1, PI3K/AKT, p38/MAPK, and Nr4a1, are implicated in the biomechanical-biochemical interplay of fibroblasts. This systematic review of the biomechanical-biochemical interplay in fibroblasts in POP not only enhances our understanding of its underlying causes but also establishes a theoretical foundation for future clinical interventions.

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“…As the most extensively studied type of epigenetic modification necessary for the regulation of gene transcription, DNA methylation is a covalent modification of the nucleotide cytosine at the 5-position (164). Although it does not alter the DNA sequence, it has an important effect on gene expression and is often associated with gene silencing (165). A study has demonstrated that DNA hypomethylation may lead to the expression of PD-L1 and inhibitory cytokines, which can be immunosuppressive (166).…”

Section: Regulation Of Pd-l1 Expression In Solid Tumors By Dna Methyl...mentioning

confidence: 99%

Epigenetic modifications: Critical participants of the PD‑L1 regulatory mechanism in solid tumors (Review)

Wang

et al. 2022

Int J Oncol

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Immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis have achieved marked and durable efficacy in patients with different solid tumors and have improved their survival. However, the presence of primary or acquired resistance to immune checkpoint blockades results in only a small fraction of patients benefiting from the treatment. An increasing number of preclinical studies have reported that PD-L1 expression in tumor cells is involved in a number of epigenetic changes, including histone modifications, non-coding RNA regulation and DNA methylation. In addition, multiple epigenetic targeting drugs have been demonstrated to directly or indirectly interfere with PD-L1 expression in various cancer models. This provides opportunities to better characterize the regulatory mechanisms of PD-L1 expression and explore novel therapeutic strategies to improve immunosuppressant response rates and overcome drug resistance. The present review focuses on the latest findings and evidence on the epigenetic mechanism regulating PD-L1 expression and discusses the biological and clinical implications of this regulatory mechanism in solid tumors. A rational combination of epigenetic regulation and PD-1/PD-L1 axis blockade may improve the prognosis of patients with solid tumors.

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DNA Methylation Malleability and Dysregulation in Cancer Progression: Understanding the Role of PARP1

Cited by 8 publications

References 273 publications

The protective effect of 17 β-estradiol on human uterosacral ligament fibroblasts from postmenopausal women with pelvic organ prolapse

The protective effect of 17 β-estradiol on human uterosacral ligament fibroblasts from postmenopausal women with pelvic organ prolapse

Roles and mechanisms of biomechanical-biochemical coupling in pelvic organ prolapse

Epigenetic modifications: Critical participants of the PD‑L1 regulatory mechanism in solid tumors (Review)

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