Identification of Cardiac Fibrosis in Young Adults With a Homozygous Frameshift Variant in <i>SERPINE1</i>

Khan, Sadiya S.; Shah, Sanjiv J.; Strande, Jennifer L.; Baldridge, Abigail S.; Flevaris, Panagiotis; Puckelwartz, Megan J.; McNally, Elizabeth M.; Rasmussen‐Torvik, Laura J.; Lee, Daniel; Carr, James C.; Benefield, Brandon; Afzal, Muhammad Bilal; Heiman, Meadow; Gupta, Sweta; Shapiro, Amy D.; Vaughan, Douglas E.

doi:10.1001/jamacardio.2020.6909

Cited by 10 publications

(5 citation statements)

References 16 publications

(23 reference statements)

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“…SERPINE1, encoding plasminogen activator inhibitor 1 (PAI-1), is an essential inhibitor of tissue plasminogen activator and urokinase (uPA). Previous studies have focused on the effect of SERPINE1 on human thrombosis, cardiac fibrosis, inflammatory injury, ageing and metabolism ( 53 – 57 ). However, current studies report on the importance of SERPINE1 in promoting tumor malignant progression, distant metastasis and chemotherapy resistance through multiple pathways.…”

Section: Discussionmentioning

confidence: 99%

BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer Cells

Liu

et al. 2022

Front. Oncol.

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BackgroundBAP1 is an important tumor suppressor involved in various biological processes and is commonly lost or inactivated in clear-cell renal cell carcinoma (ccRCC). However, the role of the BAP1-deficient tumor competing endogenous RNA (ceRNA) network involved in ccRCC remains unclear. Thus, this study aims to investigate the prognostic BAP1-related ceRNA in ccRCC.MethodsRaw data was obtained from the TCGA and the differentially expressed genes were screened to establish a BAP1-related ceRNA network. Subsequently, the role of the ceRNA axis was validated using phenotypic experiments. Dual-luciferase reporter assays and fluorescence in situ hybridization (FISH) assays were used to confirm the ceRNA network.ResultsNuclear enriched abundant transcript 1 (NEAT1) expression was significantly increased in kidney cancer cell lines. NEAT1 knockdown significantly inhibited cell proliferation and migration, which could be reversed by miR-10a-5p inhibitor. Dual-luciferase reporter assay confirmed miR-10a-5p as a common target of NEAT1 and Serine protease inhibitor family E member 1 (SERPINE1). FISH assays revealed the co-localization of NEAT1 and miR-10a-5p in the cytoplasm. Additionally, the methylation level of SERPINE1 in ccRCC was significantly lower than that in normal tissues. Furthermore, SERPINE1 expression was positively correlated with multiple immune cell infiltration levels.ConclusionsIn BAP1-deficient ccRCC, NEAT1 competitively binds to miR-10a-5p, indirectly upregulating SERPINE1 expression to promote kidney cancer cell proliferation. Furthermore, NEAT1/miR-10a-5p/SERPINE1 were found to be independent prognostic factors of ccRCC.

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Section: Discussionmentioning

confidence: 99%

BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer Cells

Liu

et al. 2022

Front. Oncol.

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“…SERPINE1 encodes plasminogen activator inhibitor-1 (PAI-1), a downstream target of heart-transforming growth factor β, which is associated with cardiac fibrosis 30 . Studies showed that a hyperosmotic, autosomal recessive cardiac fibrosis phenotype was found in young adults with homozygous migration variants of SERPINE1, suggesting that cardiac homeostasis requires an optimal range of levels of PAI-1 30 . PAI-1 is elevated in obese people with type 2 diabetes and may contribute to increased cardiovascular disease risk independently of traditional factors 31 .…”

Section: Discussionmentioning

confidence: 99%

Exploring shared therapeutic targets in diabetic cardiomyopathy and diabetic foot ulcers through bioinformatics analysis

Wu,

Yang,

Wang

et al. 2024

Sci Rep

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Advanced diabetic cardiomyopathy (DCM) patients are often accompanied by severe peripheral artery disease. For patients with DCM combined with diabetic foot ulcer (DFU), there are currently no good therapeutic targets and drugs. Here, we investigated the underlying network of molecular actions associated with the occurrence of these two complications. The datasets were downloaded from the Gene Expression Omnibus (GEO) database. We performed enrichment and protein–protein interaction analyses, and screened for hub genes. Construct transcription factors (TFs) and microRNAs regulatory networks for validated hub genes. Finally, drug prediction and molecular docking verification were performed. We identified 299 common differentially expressed genes (DEGs), many of which were involved in inflammation and lipid metabolism. 6 DEGs were identified as hub genes (PPARG, JUN, SLC2A1, CD4, SCARB1 and SERPINE1). These 6 hub genes were associated with inflammation and immune response. We identified 31 common TFs and 2 key miRNAs closely related to hub genes. Interestingly, our study suggested that fenofibrate, a lipid-lowering medication, holds promise as a potential treatment for DCM combined with DFU due to its stable binding to the identified hub genes. Here, we revealed a network involves a common target for DCM and DFU. Understanding these networks and hub genes is pivotal for advancing our comprehension of the multifaceted complications of diabetes and facilitating the development of future therapeutic interventions.

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“…MIF has been shown to promote the adhesion of leukocytes in general and T cells specifically to endothelial cells. 61 , 62 , 63 SERPINE1 has been associated with cardiac fibrosis, 64 and excessive PAI-1 levels contribute to the accumulation of collagen and other extracellular matrix proteins. This could be of potential importance in the transition from acute cellular rejection to cardiac allograft vasculopathy.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicle-Associated TWEAK Contributes to Vascular Inflammation and Remodeling During Acute Cellular Rejection

Celik

Sadrian

Grossi

et al. 2023

JACC: Basic to Translational Science

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Identification of Cardiac Fibrosis in Young Adults With a Homozygous Frameshift Variant in SERPINE1

Cited by 10 publications

References 16 publications

BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer Cells

BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer Cells

Exploring shared therapeutic targets in diabetic cardiomyopathy and diabetic foot ulcers through bioinformatics analysis

Extracellular Vesicle-Associated TWEAK Contributes to Vascular Inflammation and Remodeling During Acute Cellular Rejection

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