Hypomethylation of Notch1 DNA is associated with the occurrence of uveitis

Wei, Huixia; Yin, Xuewei; Tang, Hongying; Gao, Yanbin; Liu, Bin; Wu, Qiuxin; Tian, Qingmei; Hao, Yixian; Bi, Hongsheng

doi:10.1111/cei.13471

Cited by 10 publications

(5 citation statements)

References 46 publications

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“…Variation in DNA methylation has been widely observed in many human diseases, in-cluding autoimmune disease [47] and metabolic disorders [48], thus, DNA methylation level has also been recognized as a hallmark of cancers [49]. Currently, DNA methyla-tion level has rapidly emerged as a diagnostic and prognostic signature in many cancers because methylation level can also re ect survival outcomes.…”

Section: Discussionmentioning

confidence: 99%

microRNA-mRNA regulatory network analysis reveals a possible metastatic mechanism of uveal melanoma

zhang

Wen

Hao

et al. 2022

Preprint

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Aim: Uveal melanoma (UVM) is the most common primary intraocular malignant tumor in adults and it can develop metastatic melanoma. Therefore, it is crucial to identify biomarkers to provide early diagnosis and therapeutic targets. Methods: The differentially expressed microRNAs (DEmiRNAs) and mRNAs in patients with UVM were identified in The Cancer Genome Atlas (TCGA) database. The target mRNAs regu-lated by DEmiRNAs were obtained from TargetScan and miRDB databases. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed using Metascape software. The hub mRNAs used for the construction of protein–protein interaction (PPI) network were identified using the STRING database and CytoHub plug-in. TCGA database and miRNA-targeted mRNAs were used to identify key mRNAs. Hub and key mRNAs were searched PubMed database for verification. Survival analysis was done using Gene Expression Profiling Interactive Analysis (GEPIA). Moreover, the correlations between methylation level and key mRNA expression together with survival rate were analyzed by gene set cancer analysis (GSCA). The miRNA–mRNA network was constructed by integrating mRNAs and miRNAs in-formation. Results: We identified 22 DEmiRNAs and obtained 1436 targeted mRNAs in patients with UVM. Ten hub mRNAs (i.e., HNRNPA1, SRSF1, MATR3, SYNCRIP, TRA2B, TIAL1, FUS, FN1, SFPQ, HNRNPU) were screened and HNRNPA1, SRSF1, TRA2B, TIAL1, FUS, FN1, SFPQ, and HNRNPU were associated with cancer metastasis. KEGG analysis showed FN1 was associated with survival. In addition, CA12, NYNRIN, TDRD10 and WDR72 were associated with survival, while FOXD3, CA12 and SPDEF play pivotal roles in cancer metastasis. The TDRD10, COL11A2 and NYNRIN levels were negatively correlated with methylation, and the methylation level had a significant impact on the prognosis of metastatic UVM. The miRNA–mRNA regulatory network was con-sisted of 10 miRNAs and 14 key mRNAs, and these miRNA targets may have potential links to UVM metastasis. Conclusion: We found that HNRNPA1, SRSF1, TRA2B, TIAL1, FUS, FN1, SFPQ, HNRNPU, FOXD3, CA12 and SPDEF were related to metastatic UVM, and FN1, CA12, NYNRIN, TDRD10 and WDR72 were related to survival in metastatic UVM. These mRNAs may be used as bi-omarkers of metastatic UVM and therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

microRNA-mRNA regulatory network analysis reveals a possible metastatic mechanism of uveal melanoma

zhang

Wen

Hao

et al. 2022

Preprint

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“…Notch signaling plays an important role in inhibiting Treg differentiation and promoting Teff differentiation (67)(68)(69)(70). Exposing Tregs in vitro with JAG1 and DLL1, downstream molecules of the Notch1 pathway, has been shown to downregulate FOXP3 expression and modulate the immunosuppressive function of Tregs (71).…”

Section: Notch1mentioning

confidence: 99%

Regulatory T Cells: Therapeutic Opportunities in Uveitis

Lee

Foulsham

2022

Front. Ophthalmol.

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Regulatory T cells (Tregs) are critical for the maintenance of immune tolerance and the suppression of excessive inflammation. Many inflammatory autoimmune disorders, including autoimmune uveitis, involve the loss of the suppressive capacities of Tregs. Over the past decade, Tregs’ therapeutic potential in uveitis has garnered increasing attention. Specific subsets of Tregs, including TIGIT+ and PD-1+ Tregs, have emerged as potent immunosuppressors that may be particularly well-suited to cell-based therapeutics. Studies have elucidated the interaction between Treg development and the gut microbiome as well as various intracellular signaling pathways. Numerous cell-based therapies and therapeutic molecules have been proposed and investigated using the murine experimental autoimmune uveitis (EAU) model. However, certain challenges remain to be addressed. Studies involving the use of Tregs in human patients with uveitis are lacking, and there are concerns regarding Tregs’ production and purification for practical use, their plasticity towards inflammatory phenotypes, immunogenicity, and tumorigenicity. Nevertheless, recent research has brought Tregs closer to yielding viable treatment options for uveitis.

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“…In fact, RECK has been shown to inhibit Notch signaling in neural tissues ( 34 ) and during angiogenesis ( 62 ). An increases in the Notch signaling pathway has been implicated in several proinflammatory conditions, such as rheumatoid arthritis ( 63 ) and uveitis ( 64 ). Increased Notch activity, specifically Notch2, is known to regulate monocyte cell fate and inflammation in response to Toll Like Receptor (TLR) signaling ( 65 ).…”

Section: Reck and Inflammationmentioning

confidence: 99%

The Role of RECK in Hepatobiliary Neoplasia Reveals Its Therapeutic Potential in NASH

et al. 2021

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Non-alcoholic fatty liver disease (NAFLD) is a multimorbidity disorder ranging from excess accumulation of fat in the liver (steatosis) to steatohepatitis (NASH) and end-stage cirrhosis, and the development of hepatocellular carcinoma (HCC) in a subset of patients. The defining features of NASH are inflammation and progressive fibrosis. Currently, no pharmaceutical therapies are available for NAFLD, NASH and HCC; therefore, developing novel treatment strategies is desperately needed. Reversion Inducing Cysteine Rich Protein with Kazal motifs (RECK) is a well-known modifier of the extracellular matrix in hepatic remodeling and transition to HCC. More recently, its role in regulating inflammatory and fibrogenic processes has emerged. Here, we summarize the most relevant findings that extend our current understanding of RECK as a regulator of inflammation and fibrosis, and its induction as a potential strategy to blunt the development and progression of NASH and HCC.

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Hypomethylation of Notch1 DNA is associated with the occurrence of uveitis

Cited by 10 publications

References 46 publications

microRNA-mRNA regulatory network analysis reveals a possible metastatic mechanism of uveal melanoma

microRNA-mRNA regulatory network analysis reveals a possible metastatic mechanism of uveal melanoma

Regulatory T Cells: Therapeutic Opportunities in Uveitis

The Role of RECK in Hepatobiliary Neoplasia Reveals Its Therapeutic Potential in NASH

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