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作为神经母细胞瘤的一种潜在致癌基因和预后生物标志物。

as a potential oncogene and a prognostic biomarker for neuroblastoma.

作者信息

Song Jingjing, Ni Chao, Dong Xubin, Sheng Chenang, Qu Yue, Zhu Libin

机构信息

Department of Pediatric Surgery, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Department of Pediatric Allergy and Immunology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Front Oncol. 2022 Sep 27;12:988415. doi: 10.3389/fonc.2022.988415. eCollection 2022.

Abstract

BACKGROUND

Neuroblastoma is the most common malignant extracranial tumor for children. Molecular mechanisms underpinning the pathogenesis of this disease are yet to be fully clarified. This study aimed to identify a novel oncogene that could be used as a biomarker informing the prognosis of neuroblastoma, and to predict its biological functions, using bioinformatics and molecular biology tools.

METHODS

Three data sets from the TARGET, GSE62564, and GSE85047 databases were used for analysis. Survivals of patients with high or low expression of were compared, using the Kaplan-Meier curve and log-rank test. Immune infiltration was evaluated using ESTIMATE and MCP-counter algorithms. Synthetic small interfering RNAs (siRNAs) were employed to silence expression in neuroblastoma cell lines SH-SY5Y and SK-N-SH, in order to characterize its biological functions. Gene enrichment analyses of were carried out, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.

RESULTS

Expression of was found to significantly affect overall survival and event-free survival of patients with neuroblastoma, positively correlate with the expressions of and the gene, and negatively correlate with host immune infiltration. Expression of was elevated in patients with neuroblastoma. Silencing expression using siRNAs in SH-SY5Y and SK-N-SH resulted in decreased cell growth ( < 0.05), reduced migration ( < 0.05), and increased apoptosis ( < 0.05). Function analysis of revealed cancer-promoting effects, probably regulating several important downstream molecules, including that related to the apoptosis process and epithelial-mesenchymal transition.

CONCLUSION

We identified a potential tumor-promoting gene for neuroblastoma that could also serve as a prognostic biomarker.

摘要

背景

神经母细胞瘤是儿童最常见的颅外恶性肿瘤。该疾病发病机制的分子机制尚未完全阐明。本研究旨在利用生物信息学和分子生物学工具,鉴定一种可作为神经母细胞瘤预后生物标志物的新型癌基因,并预测其生物学功能。

方法

使用来自TARGET、GSE62564和GSE85047数据库的三个数据集进行分析。使用Kaplan-Meier曲线和对数秩检验比较高低表达患者的生存率。使用ESTIMATE和MCP-counter算法评估免疫浸润。采用合成小干扰RNA(siRNA)沉默神经母细胞瘤细胞系SH-SY5Y和SK-N-SH中的表达,以表征其生物学功能。使用基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析对进行基因富集分析。

结果

发现的表达显著影响神经母细胞瘤患者的总生存期和无事件生存期,与和基因的表达呈正相关,与宿主免疫浸润呈负相关。神经母细胞瘤患者中的表达升高。在SH-SY5Y和SK-N-SH中使用siRNA沉默表达导致细胞生长减少(<0.05)、迁移减少(<0.05)和凋亡增加(<0.05)。的功能分析显示具有促癌作用,可能调节几个重要的下游分子,包括与凋亡过程和上皮-间质转化相关的分子。

结论

我们鉴定出一种潜在的神经母细胞瘤促肿瘤基因,它也可作为一种预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f45/9552328/fd23b2a900f2/fonc-12-988415-g001.jpg

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