Screening for blood leukocyte microRNA biomarkers responsible for association between qi deficiency constitution and Pi-qi-deficiency syndrome of chronic superficial gastritis
Screening for blood leukocyte microRNA biomarkers responsible for association between qi deficiency constitution and Pi-qi-deficiency syndrome of chronic superficial gastritis
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DOI：
10.1016/j.jtcms.2018.11.003
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发表时间：
2018-10
影响因子：
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通讯作者：
Honghao Sheng;Leiming You;Xiaopu Sang;Xinhui Gao;Aijie Liu;Ting'an Li;Kunyu Li;S. Zhang;Guangrui Huang;Ting Wang;A. Xu
中科院分区：
文献类型：
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作者：
Honghao Sheng;Leiming You;Xiaopu Sang;Xinhui Gao;Aijie Liu;Ting'an Li;Kunyu Li;S. Zhang;Guangrui Huang;Ting Wang;A. Xu
目的筛选慢性浅表性胃炎（CSG）气虚质与脾气虚证相关的白细胞microRNA（miRNA）生物标志物。从白细胞中分离总RNA，并进行随后的高通量miRNA测序，以鉴定在患有PQDS的QDC和CSG患者中特异性和高度表达的miRNA。此外，还对相关miRNAs的靶基因进行了预测。对这些靶基因进行基于基因本体论（GO）和京都基因与基因组百科全书（KEGG）途径的富集分析，以进一步评估相关miRNA候选物作为负责CSG QDC和PQDS之间关联的潜在生物标志物。（P<0.05，倍数变化>1.5或<0.5），QDC和CSG PQDS患者中分别发现31和38个差异表达的miRNAs。特别地，hsa-miR-145- 5 p和hsa-miR-146 a-3 p在患有PQDS的QDC和CSG患者中均高表达。GO法分析两种常见miRNAs的靶基因，发现它们主要与合成代谢相关的功能相关，如细胞氮化合物代谢过程、生物合成过程、细胞蛋白质修饰过程、细胞组分组装等。KEGG分析确定了靶基因中富集的共同通路，包括Hippo信号通路和转录失调通路。结论Hsa-miR-145- 5 p和hsa-miR-146 a-3 p可能是CSG QDC与PQDS相关的候选生物标志物。
ObjectiveTo screen for blood leukocyte microRNA (miRNA) biomarkers responsible for the association between the traditional Chinese medicine (TCM) qi deficiency constitution (QDC) and the Pi-qi-deficiency syndrome (PQDS) of chronic superficial gastritis (CSG).MethodsPeripheral blood leukocytes were separated from people of two TCM constitutions (balance and qi deficiency) and from CSG patients with PQDS. Total RNA was isolated from the leukocytes and subjected to subsequent high-throughput miRNA sequencing to identify the miRNAs that are specifically and highly expressed in persons of QDC and CSG patients with PQDS. In addition, the target genes of the associated miRNAs were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based enrichment analyses of these target genes were performed to further evaluate the associated miRNA candidates as potential biomarkers responsible for the association between QDC and PQDS of CSG.ResultsCompared with the control group with a balance constitution (P< .05, fold change >1.5 or <0.5), 31 and 38 differentially expressed miRNAs were found in persons of QDC and CSG patients with PQDS, respectively. In particular, hsa-miR-145-5p and hsa-miR-146a-3p were highly expressed in both the persons of QDC and CSG patients with PQDS. GO analysis of the target genes of the two common miRNAs showed that they were mainly associated with functions related to synthesis and metabolism, such as cellular nitrogen compound metabolic processes, biosynthetic processes, cellular protein modification processes, and cellular component assembly. KEGG analysis identified the common pathways enriched among the target genes, including the Hippo signaling pathway and the transcriptional misregulation pathway. The common target genes of the two miRNAs seemed to be associated with the spliceosome pathway and the RNA degradation pathway.ConclusionHsa-miR-145-5p and hsa-miR-146a-3p may serve as candidate biomarkers responsible for the association between QDC and PQDS of CSG.