Genome-wide whole blood microRNAome and transcriptome analyses reveal miRNA-mRNA regulated host response to foodborne pathogen Salmonella infection in swine.

Genome-wide whole blood microRNAome and transcriptome analyses reveal miRNA-mRNA regulated host response to foodborne pathogen Salmonella infection in swine.
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DOI:
10.1038/srep12620
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发表时间:
2015-07-31
期刊:
影响因子:
4.6
通讯作者:
Guan le L
Guan le L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bao H;Kommadath A;Liang G;Sun X;Arantes AS;Tuggle CK;Bearson SM;Plastow GS;Stothard P;Guan le L

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为了理解miRNA在调节参与宿主对细菌感染的应答和食源性病原体的脱落的基因中的作用,进行了沙门氏菌攻击后来自猪全血的miRNA和mRNA的系统分析。共发现62个miRNAs在感染后差异表达(假发现率<0.1)。使用基于序列的miRNA靶标预测和miRNA-mRNA谱的负相关性对差异表达的miRNA和mRNA进行综合分析,有助于鉴定可能调节宿主对沙门氏菌感染的反应的miRNA-mRNA网络。从这些网络中,miR-214和miR-331- 3 p被鉴定为可能与沙门氏菌感染相关的新候选者。miRNA种子序列分析表明,这些miRNA调节几个关键的免疫相关基因,包括SLC 11 A1,PIGE-108A11.3和VAV 2。我们发现,攻击猪的全血中miR-214表达减少,miR-331- 3 p表达增加。此外,攻击后,miR-214(SLC 11 A1和PIGE-108A11.3)的拟定靶标的表达增加,而miR-331- 3 p(VAV 2)的拟定靶标的表达减少(通过体外测定证实的表达变化)。基于这些观察结果,我们提出了miR-214和miR-331- 3 p在调节沙门氏菌感染的免疫应答中的潜在作用。
To understand the role of miRNAs in regulating genes involved in host response to bacterial infection and shedding of foodborne pathogens, a systematic profiling of miRNAs and mRNAs from the whole blood of pigs upon Salmonella challenge was performed. A total of 62 miRNAs were differentially expressed post infection (false discovery rate <0.1). An integrative analysis of both the differentially expressed miRNAs and mRNAs using sequence-based miRNA target prediction and negative correlation of miRNA-mRNA profiles helped identify miRNA-mRNA networks that may potentially regulate host response to Salmonella infection. From these networks, miR-214 and miR-331-3p were identified as new candidates potentially associated with Salmonella infection. An miRNA seed sequence analysis suggested that these miRNAs regulate several critical immune-related genes including SLC11A1, PIGE-108A11.3 and VAV2. We showed that challenged pigs had reduced miR-214 expression and increased miR-331-3p expression in the whole blood. Furthermore, the expression of the proposed targets of miR-214 (SLC11A1 and PIGE-108A11.3) increased while that of the proposed target of miR-331-3p (VAV2) decreased following challenge (expression changes confirmed by in vitro assays). Based on these observations, we propose potential roles for miR-214 and miR-331-3p in regulation of immune responses to Salmonella infection.