VEGF (Vascular Endothelial Growth Factor) Induces NRP1 (Neuropilin-1) Cleavage via ADAMs (a Disintegrin and Metalloproteinase) 9 and 10 to Generate Novel Carboxy-Terminal NRP1 Fragments That Regulate Angiogenic Signaling

Mehta, Vedanta; Fields, Laura; Evans, Ivor H.; Yamaji, Maiko; Pellet‐Many, Caroline; Jones, Timothy; Mahmoud, Marwa; Zachary, Ian

doi:10.1161/atvbaha.118.311118

Cited by 40 publications

(26 citation statements)

References 33 publications

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“…NRP‐1 is a membrane protein that acts as a receptor for VEGF165 VEGF189 and is expressed in many types of tumors and regulates tumor cell proliferation, migration, and invasion . It is reported that the binding of VEGF and NRP‐1 has a specific effect on endothelial cell signal transduction and plays an important role in endothelial cell migration and angiogenesis . As a coreceptor of VEGF, NRP‐1 has great clinical significance.…”

Section: Discussionmentioning

confidence: 99%

The exploration of new therapeutic targets for HPV‐negative head and neck squamous cell cancer through the construction of a ceRNA network and immune microenvironment analysis

Wang

Liu

et al. 2020

J of Cellular Biochemistry

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Previous studies have shown that human papillomavirus (HPV)-negative patients with head and neck squamous cell cancer (HNSCC) suffer from an unsatisfactory prognosis. Long noncoding RNAs (lncRNAs) have been verified to participate in many biological processes, including regulating gene expression as competing endogenous RNAs (ceRNAs), while few studies focused the ceRNA network regulation mechanism in patients with HPVnegative HNSCC tumor. Meanwhile, the immune microenvironment may be critical in the development and prognosis of HPV-negative tumors. Our study aimed to further investigate the pathogenesis and potential biomarkers for the diagnosis, therapy and prognosis of HPV-negative HNSCC through a ceRNA network. Comprehensively analyzing the sequencing data of lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) in The Cancer Genome Atlas HNSCC dataset, we constructed a differentially expressed ceRNA network containing 131 lncRNAs, 35 miRNAs and 162 mRNAs. Then, survival analysis in the network was cited to explore the prognostic biomarkers. Eight mRNAs, nine lncRNAs, and one miRNA were identified to be associated with prognosis. Neuropilin (NRP) binding function, retinoid X receptor (RXR) binding, and the vascular endothelial growth factor (VEGF) signaling pathway were associated with the enrichment analysis, and they also related to the immune microenvironment. Combined with the analysis of the immune microenvironment differences, we obtained new targeted therapies using an RXR agonist, or a combination of the VEGF monoclonal antibody and an NRP antagonist, which may provide a promising future for HPV-negative HNSCC patients. K E Y W O R D S head and neck neoplasms, molecular targeted therapy, RNA, long noncoding, transcriptome, tumor microenvironment

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Section: Discussionmentioning

confidence: 99%

The exploration of new therapeutic targets for HPV‐negative head and neck squamous cell cancer through the construction of a ceRNA network and immune microenvironment analysis

Wang

Liu

et al. 2020

J of Cellular Biochemistry

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“…High expression of CD105 has been shown to disrupt angiogenesis in tumor tissue, and CD105 -BM-MSCs are more prone to differentiate into adipocytes and osteocytes 11,46 . ADAMTS9 is expressed during ossification and also may regulate angiogenic signaling induced by VEGF 47,48 . Our results together with the previous evidence suggested that the co-regulation of osteogenesis and angiogenesis by osteoblast precursor is a complex network involving multiple genes whose regulation effect sometimes are in opposite directions.…”

Section: Osteoblast Precursor Induce Angiogenesis During Coupling Witmentioning

confidence: 99%

Single-cell RNA sequencing deconvolutes thein vivoheterogeneity of human bone marrow-derived mesenchymal stem cells

Wang

Li²,

Yang

et al. 2020

Preprint

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Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stromal cells, which have a critical role in the maintenance of skeletal tissues such as bone, cartilage, and the fat found in bone marrow. In addition to providing microenvironmental support for hematopoietic processes, BM-MSCs can differentiate into various mesodermal lineages including osteoblast/osteocyte, chondrocyte, and adipocyte cells that are crucial for bone metabolism. While BM-MSCs have high cell-to-cell heterogeneity in gene expression, the cell subtypes that contribute to this heterogeneity in vivo in humans have not been characterized. To investigate the transcriptional diversity of BM-MSCs, we applied single-cell RNA sequencing (scRNA-seq) on freshly isolated CD271 + BM-derived mononuclear cells (BM-MNCs) from two human subjects. We successfully identified LEPR hi CD45 low BM-MSCs within the CD271 + BM-MNC population, and further codified the BM-MSCs into distinct subpopulations corresponding to the osteogenic, chondrogenic, and adipogenic differentiation trajectories, as well as terminal-stage quiescent cells. Biological functional annotations of transcriptomes suggest that osteoblast precursors may induce angiogenesis coupled with osteogenesis, and chondrocyte precursors may have the potential to differentiate into myocytes. We discovered transcripts for several cluster of differentiation (CD) markers that were highly expressed (e.g., CD167b, CD91, CD130 and CD118) or absent (e.g., CD74, CD217, CD148 and CD68) in BM-MSCs and could be novel markers for human BM-MSC purification. This study is the first systematic in vivo dissection of human BM-MSCs cell subtypes at the single-cell resolution, revealing insight into the extent of their cellular heterogeneity and bone homeostasis.

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“…vascular [37,38]. Elevated neuropilin-1 in urinary and renal tissues is associated with the clinical response of renal lupus nephritis [35].…”

Section: Plos Onementioning

confidence: 99%

Novel genes associated with folic acid-mediated metabolism in mouse: A bioinformatics study

Zhao

Zou

2020

PLoS ONE

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Folic acid plays an essential role in the central nervous system and cancer. This study aimed to screen genes related to folic acid metabolism. Datasets (GSE80587, GSE65267 and GSE116299) correlated to folic acid were screened in the Gene Expression Omnibus. Weighed gene co-expression network analysis was performed to identify modules associated with sample traits of folic acid and organs (brain, prostate and kidney). Functional enrichment analysis was performed for the eigengenes in modules that were significantly correlated with sample traits. Accordingly, the hub genes and key nodes in the modules were identified using the protein interaction network. A total of 17,252 genes in three datasets were identified. One module, which included 97 genes that were highly correlated with sample traits (including folic acid treatment [cor =-0.57, P = 3e-04] and kidney [cor =-0.68, p = 4e-06]), was screened out. Hub genes, including tetratricopeptide repeat protein 38 (Ttc38) and miR-185, as well as those (including Sema3A, Insl3, Dll1, Msh4 and Snai1) associated with "neuropilin binding", "regulation of reproductive process" and "vitamin D metabolic process", were identified. Genes, including Ttc38, Sema3A, Insl3, Dll1, Msh4 and Snai1, were the novel factors that may be associated with the development of the kidneys and related to folic acid treatment.

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VEGF (Vascular Endothelial Growth Factor) Induces NRP1 (Neuropilin-1) Cleavage via ADAMs (a Disintegrin and Metalloproteinase) 9 and 10 to Generate Novel Carboxy-Terminal NRP1 Fragments That Regulate Angiogenic Signaling

Abstract: Supplemental Digital Content is available in the text.

Cited by 40 publications

References 33 publications

The exploration of new therapeutic targets for HPV‐negative head and neck squamous cell cancer through the construction of a ceRNA network and immune microenvironment analysis

The exploration of new therapeutic targets for HPV‐negative head and neck squamous cell cancer through the construction of a ceRNA network and immune microenvironment analysis

Single-cell RNA sequencing deconvolutes thein vivoheterogeneity of human bone marrow-derived mesenchymal stem cells

Novel genes associated with folic acid-mediated metabolism in mouse: A bioinformatics study

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