The Neuropilin-1 Ligand,Sema3A,Acts as a Tumor Suppressor in the Pathogenesis of Acute Leukemia |
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Authors: | Zhi-Gang Yang Rui-Ting Wen Kai Qi Jun Li Gui-Xian Zheng Yu-Feng Wang Yun-Guang Hong Yu-Ming Zhang |
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Institution: | 1. Department of Hematology, Affiliated Central People's Hospital of Zhanjiang of Guangdong Medical University, Zhanjiang, Guangdong, 524045 People's Republic of China;2. Department of Hematology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001 People's Republic of China;3. Laboratory of Hematology, Guangdong Medical University, Zhanjiang, Guangdong, 524023 People's Republic of China |
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Abstract: | Semaphorin-3A (Sema3A) and vascular endothelial growth factor (VEGF165) are ligands of neuropilin-1 (NRP-1 or CD304) and are related to immunoregulation and tumor angiogenesis, respectively. However, possible interactions between NRP-1 and Sema3A and VEGF165 in acute leukemia remain unclear, especially whether Sema3A plays a role in acute leukemia. In this study, both of the proportion of regulatory T cells (Tregs) and their expression of NRP-1 were found to increase in acute leukemia patients compared with healthy controls. In contrast, lower mRNA and plasma levels of Sema3A were detected in the acute leukemia patients. In vitro, the addition of exogenous Sema3A inhibited the expression of NRP-1 on Tregs and it promoted apoptosis of leukemia cells. However, in the presence of anti-Sema3A antibody, the effect of rhSema3A on NRP-1 expression was reversed. These results suggest that Sema3A promotes apoptosis in leukemia cells by inhibiting expression of NRP-1, and thus, represents a tumor suppressor protein with a role in the pathogenesis of acute leukemia. Consequently, NRP-1/Sema3A signaling may represent a novel target for the treatment of acute leukemia and should be further studied. Anat Rec, 302:1127–1135, 2019. © 2018 Wiley Periodicals, Inc. |
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Keywords: | NRP-1 Sema3A VEGF165 acute leukemia |
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