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Nectin2 influences cell apoptosis by regulating ANXA2 expression in neuroblastoma
Shihan Zhang1, Chiyi Jiang1, Yan Su1
1Medical 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.
Acta Biochimica Et Biophysica Sinica
|March 14, 2023
Summary
Elevated Nectin2 levels correlate with poorer outcomes in neuroblastoma (NB), a pediatric cancer. Targeting Nectin2 may offer a new gene therapy approach for NB patients.
Area of Science:
- Oncology
- Molecular Biology
- Pediatric Cancer Research
Background:
- Neuroblastoma (NB) is the most common infant solid cancer, originating from the peripheral sympathetic nervous system.
- Nectin2, an immunoglobulin superfamily member, is implicated in cancer development.
Purpose of the Study:
- To investigate the role of Nectin2 in neuroblastoma progression.
- To evaluate Nectin2 as a potential therapeutic target for NB.
Main Methods:
- Serum Nectin2 levels were measured in NB patients and healthy controls.
- Nectin2 knockdown was performed in NB cell lines (SH-SY5Y, SK-N-BE2).
- RNA-sequencing, qRT-PCR, and Western blot analyses were used to assess gene expression changes and protein levels.
Main Results:
- Serum Nectin2 levels were higher in NB patients and correlated with advanced INSS stage and shorter survival.
- Nectin2 knockdown inhibited NB cell migration, induced apoptosis, and caused cell cycle arrest.
- Nectin2 knockdown altered the expression of 258 genes, including a decrease in ANXA2 expression.
- ANXA2 overexpression rescued NB cell apoptosis and modulated cleaved caspase3, BAX, MMP2, and MMP9 expression.
Conclusions:
- Nectin2 plays a significant role in neuroblastoma progression.
- Nectin2 is a potential biomarker for NB staging and prognosis.
- Nectin2 inhibition, potentially via gene therapy, warrants further investigation for NB treatment.
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