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通过分析血清微小RNA表达鉴定与弥漫性大B细胞淋巴瘤相关的关键微小RNA

Identification of key microRNAs associated with diffuse large B-cell lymphoma by analyzing serum microRNA expressions.

作者信息

Meng Yuanyuan, Quan Lina, Liu Aichun

机构信息

Department of Gynecology Tumor, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Harbin, Heilongjiang 150080, China.

Department of Hematology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Harbin, Heilongjiang 150080, China.

出版信息

Gene. 2018 Feb 5;642:205-211. doi: 10.1016/j.gene.2017.11.022. Epub 2017 Nov 8.

Abstract

PURPOSE

This study aimed to investigate the molecular mechanism underlying diffuse large B-cell lymphoma (DLBCL).

METHODS

Serum miRNA expression analysis for the serum samples of patients with DLBCL and those of controls was performed using the Illumina sequencing technology. Differentially expressed miRNAs (DEMs) were identified on the basis of the sequencing data. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and protein-protein interaction (PPI) network construction for the target genes of DEMs were also conducted. Moreover, the selected DEMs were verified using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR).

RESULTS

Fifty-one DEMs were identified between DLBCL disease and control groups, of which two were upregulated and 49 were downregulated. In total, 3631 target genes of DEMs were obtained, and hsa-miR-34a-5p had the most target genes. Among the 51 DEMs, 19 were significantly enriched in 41 KEGG pathways. hsa-miR-34a-5p was enriched in 15 pathways such as the p53 signaling pathway. hsa-miR-323b-3p was enriched in four pathways such as pathways in cancer. The PPI network revealed that hsa-miR-34a-5p had the most target genes such as tumor protein p53 (TP53), and hsa-miR-431-5p regulated tyrosine protein kinase Fyn (FYN). Furthermore, qRT-PCR results showed that hsa-miR-34a-5p was upregulated, whereas hsa-miR-323b-3p and hsa-miR-431-5p were downregulated.

CONCLUSION

hsa-miR-34a-5p may be directly regulated by TP53 and may be involved in DLBCL development via the p53 signaling pathway. Furthermore, hsa-miR-323b-3p may be related to DLBCL by participating in pathways in cancer. hsa-miR-431-5p may also play a role in DLBCL by regulating FYN.

摘要

目的

本研究旨在探究弥漫性大B细胞淋巴瘤(DLBCL)的分子机制。

方法

采用Illumina测序技术对DLBCL患者及对照者的血清样本进行血清miRNA表达分析。根据测序数据鉴定差异表达的miRNA(DEM)。还对DEM的靶基因进行京都基因与基因组百科全书(KEGG)通路富集分析及蛋白质-蛋白质相互作用(PPI)网络构建。此外,使用实时定量逆转录聚合酶链反应(qRT-PCR)对所选DEM进行验证。

结果

在DLBCL疾病组和对照组之间鉴定出51个DEM,其中2个上调,49个下调。共获得3631个DEM的靶基因,hsa-miR-34a-5p的靶基因最多。在51个DEM中,19个在41条KEGG通路中显著富集。hsa-miR-34a-5p在15条通路中富集,如p53信号通路。hsa-miR-323b-3p在4条通路中富集,如癌症相关通路。PPI网络显示hsa-miR-34a-5p的靶基因最多,如肿瘤蛋白p53(TP53),hsa-miR-431-5p调节酪氨酸蛋白激酶Fyn(FYN)。此外,qRT-PCR结果显示hsa-miR-34a-5p上调,而hsa-miR-323b-3p和hsa-miR-431-5p下调。

结论

hsa-miR-34a-5p可能受TP53直接调控,并可能通过p53信号通路参与DLBCL的发生发展。此外,hsa-miR-323b-3p可能通过参与癌症相关通路与DLBCL相关。hsa-miR-431-5p也可能通过调节FYN在DLBCL中发挥作用。

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