Nectin2 influences cell apoptosis by regulating ANXA2 expression in neuroblastoma

Neuroblastoma (NB) is a pediatric cancer of the peripheral sympathetic nervous system and represents the most frequent solid malignancy in infants. Nectin2 belongs to the immunoglobulin superfamily and has been shown to play a role in tumorigenesis. In the current study, we demonstrate that serum Ne...

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Main Authors: Zhang Shihan, Jiang Chiyi, Su Yan, Gui Jingang, Yue Zhixia, Jian Binglin, He Sidou, Ma Xiaoli
Format: Article
Language:English
Published: China Science Publishing & Media Ltd. 2023-03-01
Series:Acta Biochimica et Biophysica Sinica
Subjects:
Online Access:https://www.sciengine.com/doi/10.3724/abbs.2023020
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author Zhang Shihan
Jiang Chiyi
Su Yan
Gui Jingang
Yue Zhixia
Jian Binglin
He Sidou
Ma Xiaoli
author_facet Zhang Shihan
Jiang Chiyi
Su Yan
Gui Jingang
Yue Zhixia
Jian Binglin
He Sidou
Ma Xiaoli
author_sort Zhang Shihan
collection DOAJ
description Neuroblastoma (NB) is a pediatric cancer of the peripheral sympathetic nervous system and represents the most frequent solid malignancy in infants. Nectin2 belongs to the immunoglobulin superfamily and has been shown to play a role in tumorigenesis. In the current study, we demonstrate that serum Nectin2 level is increased in NB patients compared with that in healthy controls and Nectin2 level is correlated with neuroblastoma international neuroblastoma staging system (INSS) classification. There is a positive correlation between Nectin2 level and shorter overall survival in NB patients. Knockdown of Nectin2 reduces the migration of SH-SY5Y and SK-N-BE2 cells and induces their apoptosis and cell cycle arrest. RNA-seq analysis demonstrates that Nectin2 knockdown affects the expressions of 258 genes, including 240 that are upregulated and 18 that are downregulated compared with negative controls. qRT-PCR and western blot analysis confirm that ANXA2 expression is decreased in Nectin2-knockdown SH-SY5Y cells, consistent with the RNA-seq results. ANXA2 overexpression rescues the percentage of apoptotic NB cells induced by Nectin2 knockdown and compensates for the impact of Nectin2 knockdown on cleaved caspase3 and bax expressions. In addition, western blot analysis results show that ANXA2 overexpression rescues the effect of Nectin2 knockdown on MMP2 and MMP9 expressions. The current data highlight the importance of Nectin2 in NB progression and the potential of Nectin2 as a novel candidate target for gene therapy.
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spelling doaj.art-709bc4ec9ed74a3895509b70786dfb072023-11-06T08:51:40ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452023-03-015535636610.3724/abbs.202302020d259ccNectin2 influences cell apoptosis by regulating ANXA2 expression in neuroblastomaZhang Shihan0Jiang Chiyi1Su Yan2Gui Jingang3Yue Zhixia4Jian Binglin5He Sidou6Ma Xiaoli7["Medical Oncology Department, Pediatric Oncology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Clinical Discipline of Pediatric Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing 100045, China"]["Medical Oncology Department, Pediatric Oncology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Clinical Discipline of Pediatric Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing 100045, China"]["Medical Oncology Department, Pediatric Oncology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Clinical Discipline of Pediatric Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing 100045, China"]["Laboratory of Tumor Immunology Beijing Pediatric Research Institute Beijing Children’s Hospital Capital Medical University National Center for Children’s Health, Beijing 100045, China"]["Medical Oncology Department, Pediatric Oncology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Clinical Discipline of Pediatric Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing 100045, China"]["Medical Oncology Department, Pediatric Oncology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Clinical Discipline of Pediatric Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing 100045, China"]["Medical Oncology Department, Pediatric Oncology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Clinical Discipline of Pediatric Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing 100045, China"]["Medical Oncology Department, Pediatric Oncology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Clinical Discipline of Pediatric Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing 100045, China"]Neuroblastoma (NB) is a pediatric cancer of the peripheral sympathetic nervous system and represents the most frequent solid malignancy in infants. Nectin2 belongs to the immunoglobulin superfamily and has been shown to play a role in tumorigenesis. In the current study, we demonstrate that serum Nectin2 level is increased in NB patients compared with that in healthy controls and Nectin2 level is correlated with neuroblastoma international neuroblastoma staging system (INSS) classification. There is a positive correlation between Nectin2 level and shorter overall survival in NB patients. Knockdown of Nectin2 reduces the migration of SH-SY5Y and SK-N-BE2 cells and induces their apoptosis and cell cycle arrest. RNA-seq analysis demonstrates that Nectin2 knockdown affects the expressions of 258 genes, including 240 that are upregulated and 18 that are downregulated compared with negative controls. qRT-PCR and western blot analysis confirm that ANXA2 expression is decreased in Nectin2-knockdown SH-SY5Y cells, consistent with the RNA-seq results. ANXA2 overexpression rescues the percentage of apoptotic NB cells induced by Nectin2 knockdown and compensates for the impact of Nectin2 knockdown on cleaved caspase3 and bax expressions. In addition, western blot analysis results show that ANXA2 overexpression rescues the effect of Nectin2 knockdown on MMP2 and MMP9 expressions. The current data highlight the importance of Nectin2 in NB progression and the potential of Nectin2 as a novel candidate target for gene therapy. https://www.sciengine.com/doi/10.3724/abbs.2023020neuroblastomaNectin2apoptosisANXA2
spellingShingle Zhang Shihan
Jiang Chiyi
Su Yan
Gui Jingang
Yue Zhixia
Jian Binglin
He Sidou
Ma Xiaoli
Nectin2 influences cell apoptosis by regulating ANXA2 expression in neuroblastoma
Acta Biochimica et Biophysica Sinica
neuroblastoma
Nectin2
apoptosis
ANXA2
title Nectin2 influences cell apoptosis by regulating ANXA2 expression in neuroblastoma
title_full Nectin2 influences cell apoptosis by regulating ANXA2 expression in neuroblastoma
title_fullStr Nectin2 influences cell apoptosis by regulating ANXA2 expression in neuroblastoma
title_full_unstemmed Nectin2 influences cell apoptosis by regulating ANXA2 expression in neuroblastoma
title_short Nectin2 influences cell apoptosis by regulating ANXA2 expression in neuroblastoma
title_sort nectin2 influences cell apoptosis by regulating anxa2 expression in neuroblastoma
topic neuroblastoma
Nectin2
apoptosis
ANXA2
url https://www.sciengine.com/doi/10.3724/abbs.2023020
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AT suyan nectin2influencescellapoptosisbyregulatinganxa2expressioninneuroblastoma
AT guijingang nectin2influencescellapoptosisbyregulatinganxa2expressioninneuroblastoma
AT yuezhixia nectin2influencescellapoptosisbyregulatinganxa2expressioninneuroblastoma
AT jianbinglin nectin2influencescellapoptosisbyregulatinganxa2expressioninneuroblastoma
AT hesidou nectin2influencescellapoptosisbyregulatinganxa2expressioninneuroblastoma
AT maxiaoli nectin2influencescellapoptosisbyregulatinganxa2expressioninneuroblastoma