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基于新型生物信息学模型的儿童急性髓系白血病微小RNA生物标志物鉴定

MicroRNA biomarker identification for pediatric acute myeloid leukemia based on a novel bioinformatics model.

作者信息

Yan Wenying, Xu Lihua, Sun Zhandong, Lin Yuxin, Zhang Wenyu, Chen Jiajia, Hu Shaoyan, Shen Bairong

机构信息

Center for Systems Biology, Soochow University, Suzhou, 215006, China.

Taicang Center for Translational Bioinformatics, Taicang 215400, China.

出版信息

Oncotarget. 2015 Sep 22;6(28):26424-36. doi: 10.18632/oncotarget.4459.

Abstract

Acute myeloid leukemia (AML) in children is a complex and heterogeneous disease. The identification of reliable and stable molecular biomarkers for diagnosis, especially early diagnosis, remains a significant therapeutic challenge. Aberrant microRNA expression could be used for cancer diagnosis and treatment selection. Here, we describe a novel bioinformatics model for the prediction of microRNA biomarkers for the diagnosis of paediatric AML based on computational functional analysis of the microRNA regulatory network substructure. microRNA-196b, microRNA-155 and microRNA-25 were identified as putative diagnostic biomarkers for pediatric AML. Further systematic analysis confirmed the association of the predicted microRNAs with the leukemogenesis of AML. In vitro q-PCR experiments showed that microRNA-155 is significantly overexpressed in children with AML and microRNA-196b is significantly overexpressed in subgroups M4-M5 of the French-American-British classification system. These results suggest that microRNA-155 is a potential diagnostic biomarker for all subgroups of paediatric AML, whereas microRNA-196b is specific for subgroups M4-M5.

摘要

儿童急性髓系白血病(AML)是一种复杂的异质性疾病。识别可靠且稳定的分子生物标志物用于诊断,尤其是早期诊断,仍然是一项重大的治疗挑战。异常的微小RNA表达可用于癌症诊断和治疗选择。在此,我们基于微小RNA调控网络子结构的计算功能分析,描述了一种用于预测小儿AML诊断的微小RNA生物标志物的新型生物信息学模型。微小RNA-196b、微小RNA-155和微小RNA-25被鉴定为小儿AML的潜在诊断生物标志物。进一步的系统分析证实了预测的微小RNA与AML白血病发生的关联。体外定量聚合酶链反应(q-PCR)实验表明,微小RNA-155在AML患儿中显著过表达,而微小RNA-196b在法国-美国-英国分类系统的M4-M5亚组中显著过表达。这些结果表明,微小RNA-155是小儿AML所有亚组的潜在诊断生物标志物,而微小RNA-196b对M4-M5亚组具有特异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf1/4694912/b4c92679748d/oncotarget-06-26424-g001.jpg

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