The Neuropilin‐1 Ligand, Sema3A, Acts as a Tumor Suppressor in the Pathogenesis of Acute Leukemia

Yang, Zhigang; Wen, Ruiting; Qi, Kai; Li, Jun; Zheng, Guixian; Wang, Yufeng; Hong, Yun-Guang; Zhang, Yuming

doi:10.1002/ar.24016

Cited by 15 publications

(10 citation statements)

References 25 publications

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“…Indeed, it was recently reported that a mutated sema3A, that unlike natural sema3A binds directly to the plexin-A4 receptor and not to neuropilin-1, is a better inhibitor of angiogenesis as compared to wild type sema3A and strongly inhibits the progression of pancreatic cancer in mouse models [89]. Interestingly, it was recently found that sema3A may also function as an inhibitor of the development of hematological malignancies such as multiple myeloma and various forms of leukemia and that this activity is likely also due to its anti-angiogenic activity [90,91,92].…”

Section: Class-3 Semaphorins As Regulators Of Tumor Progressionmentioning

confidence: 99%

Class-3 Semaphorins and Their Receptors: Potent Multifunctional Modulators of Tumor Progression

Toledano

Nir-Zvi

Engelman

et al. 2019

IJMS

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Semaphorins are the products of a large gene family containing 28 genes of which 21 are found in vertebrates. Class-3 semaphorins constitute a subfamily of seven vertebrate semaphorins which differ from the other vertebrate semaphorins in that they are the only secreted semaphorins and are distinguished from other semaphorins by the presence of a basic domain at their C termini. Class-3 semaphorins were initially characterized as axon guidance factors, but have subsequently been found to regulate immune responses, angiogenesis, lymphangiogenesis, and a variety of additional physiological and developmental functions. Most class-3 semaphorins transduce their signals by binding to receptors belonging to the neuropilin family which subsequently associate with receptors of the plexin family to form functional class-3 semaphorin receptors. Recent evidence suggests that class-3 semaphorins also fulfill important regulatory roles in multiple forms of cancer. Several class-3 semaphorins function as endogenous inhibitors of tumor angiogenesis. Others were found to inhibit tumor metastasis by inhibition of tumor lymphangiogenesis, by direct effects on the behavior of tumor cells, or by modulation of immune responses. Notably, some semaphorins such as sema3C and sema3E have also been found to potentiate tumor progression using various mechanisms. This review focuses on the roles of the different class-3 semaphorins in tumor progression.

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Section: Class-3 Semaphorins As Regulators Of Tumor Progressionmentioning

confidence: 99%

Class-3 Semaphorins and Their Receptors: Potent Multifunctional Modulators of Tumor Progression

Toledano

Nir-Zvi

Engelman

et al. 2019

IJMS

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“…Neuropilin-1 (NRP1) is a trans-membrane glycoprotein that function as a co-receptor for multiple extracellular ligands such as semaphorins, hepatic growth factor, FGF and TGF-β 5,6 . Mounting evidence has showed that NRP1 exert a critical role in tumorigenesis and metastasis 7,8 .…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-19b-3p suppresses gastric cancer development by negatively regulating Neuropilin-1

Wei¹,

Guo²,

Tang³

et al. 2020

Preprint

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Background Gastric cancer (GC) remains one of the most common digestive malignancies worldwide and ranked third causes of cancer-related death. Mounting evidence has revealed that miRNAs exert critical regulatory roles in GC development. Methods Immunohistochemistry (IHC) and western blot assay were performed to determine the protein expression levels of neuropilin-1 (NRP1) and mRNA levels were confirmed by quantitative RT-PCR (qRT-PCR) in GC tissues. Kaplan–Meier analysis was performed to evaluate the prognostic value of NRP1 in GC. Knockdown of NRP1 was conducted to analyse its function in vitro and vivo. Luciferase reporter assay, western blot and qRT-qPCR were employed to identify the miRNAs which directly targeted NRP1. Furthermore, Bioinformatics analysis and experimental verification were used to explore the potential molecular mechanism and signaling pathway. Results In the current study, we revealed that neuropilin-1 (NRP1) was highly expressed in GC tumor tissues and was associated with poor prognosis in GC patients. NRP1 knockdown inhibited GC cell growth, migration and invasion in vitro, while suppressed GC xenograft tumor development in vivo. Bioinformatics analysis predicted that miR-19b-3p down-regulated NRP1 expression by targeting its 3’-UTR. Functional assay demonstrated that miR-19b-3p inhibited GC cell growth, migration and invasion via negatively regulating NRP1. Overexpression NRP1 partially reversed the regulatory effect of miR-19b-3p. Moreover, we showed that miR-19b-3p/NRP1 axis regulated the epithelial-to-mesenchymal transition and focal adhesion in GC, which might contribute the GC development and progression. Conclusions Taken together, our findings suggest a regulatory network of miR-19b-3p/NRP1 in GC development. The miR-19b-3p/NRP1 axis might be further explored as a potential diagnostic and therapeutic target in GC.

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“…Folic acid deficiency correlates with elevated homocysteine levels, which is a risk factor for colon cancer [ 1 , 32 ]. Larriba et al [ 33 ] reported that colon cancer tissues that co-express Snai2 and Snai1 downregulated the vitamin D receptor, which mediates the antitumoral action of vitamin D. Sema3A is a ligand of neuropilin-1 and a tumor suppressor in acute leukemia [ 34 ]. Neuropilin-1 is involved in diverse processes, including cancer and angiogenesis [ 35 – 37 ].…”

Section: Discussionmentioning

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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The Neuropilin‐1 Ligand, Sema3A, Acts as a Tumor Suppressor in the Pathogenesis of Acute Leukemia

Cited by 15 publications

References 25 publications

Class-3 Semaphorins and Their Receptors: Potent Multifunctional Modulators of Tumor Progression

Class-3 Semaphorins and Their Receptors: Potent Multifunctional Modulators of Tumor Progression

MicroRNA-19b-3p suppresses gastric cancer development by negatively regulating Neuropilin-1

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

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