Long non-coding RNA MEG3 and its genetic variant rs941576 are associated with rheumatoid arthritis pathogenesis in Egyptian patients

Wahba, Alaa Samir; Ibrahim, Maha; Mesbah, Noha M.; Saleh, Samy M.; Abo-Elmatty, Dina M.; Mehanna, Eman T.

doi:10.1080/13813455.2020.1784951

Cited by 23 publications

(18 citation statements)

References 40 publications

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“…It was demonstrated that reduced blood and oxygen supply to the cells induces apoptosis due cellular energy deficiency, however persistent exposure to hypoxic conditions drives the cells to adapt to these conditions and to promote anti-apoptotic pathways through enhanced anti-apoptotic proteins expression including increase in Bcl-2 and Mcl-1 and attenuated pro-apoptotic proteins expression including BAX and Bid in a HIF-1 independent manner [55]. A growing body of evidence indicates that RA-FLSs are resistant to apoptosis and exhibit altered mitochondrial pathways of apoptosis, regulated by Bcl-2 family of proteins [4]. Previous studies demonstrated elevated expression of anti-apoptotic proteins Bcl-2 and Mcl-1 [56], and on the other hand, decreased proapoptotic proteins levels such as BAX in RA-FLS [57].…”

Section: Discussionmentioning

confidence: 99%

“…Clinical synovitis is characterized by augmented vascular permeability and infiltration of inflammatory cells into the synovium. As a result, fibroblast-like synoviocytes (FLSs) acquire an altered phenotype secreting a diverse array of proinflammatory cytokines, chemokines, and matrix metalloproteinases (MMPs), leading to chronic inflammation, synovial hyperplasia, and progressive joint and cartilage destruction and resultant disability [4]. Interestingly, adipocytokines, including adipokines, cytokines, chemokines, and complementary factors are involved in regulation of glucose and lipid metabolism, blood pressure, and modulation of immune response and inflammation, and thus, are implicated in various physiological and pathological processes [5,6].…”

Section: Introductionmentioning

confidence: 99%

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Association of the Adipokines Chemerin, Apelin, Vaspin and Omentin and Their Functional Genetic Variants with Rheumatoid Arthritis

Wahba

Ibrahim

Abo-Elmatty

et al. 2021

JPM

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Adipokines were shown to exert crucial roles in rheumatic diseases. This study aimed to assess the role of chemerin, apelin, vaspin, and omentin adipokines and their genetic variants rs17173608, rs2235306, rs2236242, and rs2274907, respectively, in rheumatoid arthritis (RA) pathogenesis in Egyptian patients. A total of 150 RA patients and 150 healthy individuals were recruited. Blood samples were collected and used for genotyping. Serum was separated and used for expression analysis by quantitative PCR, and various biochemical markers determination by ELISA. Serum protein levels of chemerin and vaspin, as well as their gene expression levels were higher, while those of apelin and omentin were lower in RA patients and were associated with most of RA clinical and laboratory characteristics. G allele of chemerin rs17173608, T allele of vaspin rs2236242, and T allele of omentin rs2274907 were more frequent in RA patients. Serum levels and gene expression levels of chemerin in GG genotype carriers and vaspin in TT genotype group were significantly higher, while those of omentin in TT genotype carriers were significantly lower than RA patients with other genotypes. There was no association between apelin rs2235306 and RA. Chemerin rs17173608, vaspin rs2236242, and omentin rs2274907 polymorphisms were associated with increased susceptibility to RA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of the Adipokines Chemerin, Apelin, Vaspin and Omentin and Their Functional Genetic Variants with Rheumatoid Arthritis

Wahba

Ibrahim

Abo-Elmatty

et al. 2021

JPM

Self Cite

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“…The low expression of MEG3 in RA patients was negatively correlated with HIF-1α and vascular endothelial growth factor A (VEGF) serum level, and positively correlated with BAX. The polymorphism of MEG3 gene rs941576 (A/G) has been confirmed to be associated with the increased severity of RA in the current population (Wahba et al, 2020).…”

Section: Lncrnas In Chondrocytesmentioning

confidence: 66%

Dysregulation of lncRNAs in Rheumatoid Arthritis: Biomarkers, Pathogenesis and Potential Therapeutic Targets

et al. 2021

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Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology, mainly manifested by persistent abnormal proliferation of fibroblast-like synoviocytes (FLSs), inflammation, synovial hyperplasia and cartilage erosion, accompanied by joint swelling and joint destruction. Abnormal expression or function of long noncoding RNAs (lncRNAs) are closely related to human diseases, including cancers, mental diseases, autoimmune diseases and others. The abnormal sequence and spatial structure of lncRNAs, the disorder expression and the abnormal interaction with the binding protein will lead to the change of gene expression in the way of epigenetic modification. Increasing evidence demonstrated that lncRNAs were involved in the activation of FLSs, which played a key role in the pathogenesis of RA. In this review, the research progress of lncRNAs in the pathogenesis of RA was systematically summarized, including the role of lncRNAs in the diagnosis of RA, the regulatory mechanism of lncRNAs in the pathogenesis of RA, and the intervention role of lncRNAs in the treatment of RA. Furthermore, the activated signal pathways, the role of DNA methylation and other mechanism have also been overview in this review.

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“…For example, the genetic variant rs941576 lies within a conserved and regulatory region within intron 6 of the maternally expressed Meg3 (Figure 3C). It has been suggested that rs941576 is strongly associated with T1D susceptibility and rheumatoid arthritis (Wallace et al 2010;Wahba et al 2020) . Our data show that this SNP in the mouse genome lies within a peak linked to Dlk1 .…”

Section: Identification Of Cell Type-specific Tfs In Immune Cellsmentioning

confidence: 99%

The single-cell epigenetic regulatory landscape in mammalian perinatal testis development

Liao

et al. 2021

Preprint

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Spermatogenesis depends on an orchestrated series of developing events in germ cells and full maturation of the somatic microenvironment. To date, the majority of efforts to study cellular heterogeneity in testis has been focused on single-cell gene expression rather than the chromatin landscape shaping gene expression. To advance our understanding of the regulatory programs underlying testicular cell types, we analyzed single-cell chromatin accessibility profiles in more than 25,000 cells from mouse developing testis. We showed that scATAC-Seq allowed us to deconvolve distinct cell populations and identify cis-regulatory elements (CREs) underlying cell type specification. We identified sets of transcription factors associated with cell type-specific accessibility, revealing novel regulators of cell fate specification and maintenance. Pseudotime reconstruction revealed detailed regulatory dynamics coordinating the sequential developmental progressions of germ cells and somatic cells. This high-resolution data also revealed putative stem cells within the Sertoli and Leydig cell populations. Further, we defined candidate target cell types and genes of several GWAS signals, including those associated with testosterone levels and coronary artery disease. Collectively, our data provide a blueprint of the ‘regulon’ of the mouse male germline and supporting somatic cells.

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Long non-coding RNA MEG3 and its genetic variant rs941576 are associated with rheumatoid arthritis pathogenesis in Egyptian patients

Cited by 23 publications

References 40 publications

Association of the Adipokines Chemerin, Apelin, Vaspin and Omentin and Their Functional Genetic Variants with Rheumatoid Arthritis

Association of the Adipokines Chemerin, Apelin, Vaspin and Omentin and Their Functional Genetic Variants with Rheumatoid Arthritis

Dysregulation of lncRNAs in Rheumatoid Arthritis: Biomarkers, Pathogenesis and Potential Therapeutic Targets

The single-cell epigenetic regulatory landscape in mammalian perinatal testis development

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