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微小RNA及其靶基因在人类多发性骨髓瘤中的潜在作用。

Potential roles of microRNAs and their target genes in human multiple myeloma.

作者信息

Yang Yong, Lin Jisheng, Ma Zhao, Li Jinjun, Li Dong, Wang Bingqiang, Fei Qi

机构信息

Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

出版信息

Eur J Haematol. 2017 Aug;99(2):178-185. doi: 10.1111/ejh.12901. Epub 2017 Jun 2.

Abstract

OBJECTIVES

The etiology of multiple myeloma (MM) is unknown and it remains incurable. We sought to elucidate the mechanisms underlying miRNAs involvement in MM pathogenesis.

METHODS

Public mRNA and miRNA expression datasets for MM were collected from the Gene Expression Omnibus database. By integrated bioinformatics analysis, the expression signatures were identified and the miRNA-mRNA interaction network was constructed. The potential functions of target genes were then explored by functional enrichment analysis.

RESULTS

Totally, 839 differentially expressed mRNAs and six differentially expressed miRNAs were identified. The context of miRNAs-mediated genes regulatory network consisted of 288 possible miRNA-mRNA target pairs. The hub miRNA was hsa-miR-92a, which can serve as the indicator for MM disease status. Another miRNA, hsa-miR-148a, could be useful for prognosis of MM. Functional annotation revealed that the miRNA targets may play important roles in viral infection and proteasome. Moreover, miRNA targets may be involved in renal cell carcinoma and other nervous system disease such as Huntington's disease, Alzheimer's disease and Parkinson's disease, which may be subsequent complications of MM.

CONCLUSIONS

Infections could be a leading cause for the morbidity of MM patients. The crucial protein degradation machinery may be essential in the pathogenesis of MM.

摘要

目的

多发性骨髓瘤(MM)的病因不明且仍无法治愈。我们试图阐明miRNA参与MM发病机制的潜在机制。

方法

从基因表达综合数据库收集MM的公共mRNA和miRNA表达数据集。通过综合生物信息学分析,识别表达特征并构建miRNA-mRNA相互作用网络。然后通过功能富集分析探索靶基因的潜在功能。

结果

共鉴定出839个差异表达的mRNA和6个差异表达的miRNA。miRNA介导的基因调控网络由288个可能的miRNA-mRNA靶标对组成。核心miRNA是hsa-miR-92a,可作为MM疾病状态的指标。另一种miRNA,hsa-miR-148a,可能对MM的预后有用。功能注释显示,miRNA靶标可能在病毒感染和蛋白酶体中起重要作用。此外,miRNA靶标可能参与肾细胞癌和其他神经系统疾病,如亨廷顿舞蹈病、阿尔茨海默病和帕金森病,这些可能是MM的后续并发症。

结论

感染可能是MM患者发病的主要原因。关键的蛋白质降解机制可能在MM的发病机制中至关重要。

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