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通过整合微小RNA过表达和微阵列数据,使用TargetScore来揭示银屑病中miRNA203和miRNA - 146a的潜在靶点。

TargetScore used to reveal potential targets of miRNA203 and miRNA-146a in psoriasis by integrating microRNA overexpression and microarray data.

作者信息

Chen Hai-Xia, Liu Yan-Song, Zhang Xiu-Jie

机构信息

Department of Dermatology, People's Hospital of Rizhao, Rizhao.

Department of Dermatology, Jinan Dermatosis Prevention and Control Hospital.

出版信息

Medicine (Baltimore). 2018 Oct;97(41):e12671. doi: 10.1097/MD.0000000000012671.

Abstract

OBJECTIVE

Systematic tracking of microRNA (miRNA) targets remains a challenge. In our work, we aimed to use TargetScore to investigate the potential targets of miRNA203 and miRNA-146a in psoriasis by integrating miRNA overexpression information and sequence data, and to further uncover the functions of miRNA203 and miRNA-146a in psoriasis.

METHODS

This was a case-control bioinformatics analysis using already published microarray data of psoriasis. We calculated targetScores by combining log fold-change and sequence scores obtained from TargetScan context score, probabilities of conserved targeting, and derived the distribution of targetScores. The scoring cutoff was chosen based on the different targetScore distributions for the nonvalidated and validated targets. The potential target genes for miRNA-203 and miRNA-146a were predicted based on the targetScore threshold. To reveal the functions of miRNA-203 and miRNA-146a, we implemented pathway enrichment analyses for the targets of miRNA-203 and miRNA-146a.

RESULTS

TargetScore >0.4 was selected as the threshold to filter out less confidence targets because we observed little overlap between the 2 distribution at targetScore = 0.4. Based on the targetScore >0.4, 49 target genes for miRNA-203 and 17 targets for miRNA-146a were identified. Pathway enrichment results showed that the target genes of miRNA-203 (including KIR2DL1, HLA-DQA1, KIR3DL1) only participated in antigen processing and presentation. The target genes of miRNA-146a (covering ADORA3, CYSLTR2, HRH4) were only involved in neuroactive ligand-receptor interaction.

CONCLUSION

MiRNA203 and miRNA-146a played important roles in psoriasis progression, partially through regulating the pathways of antigen processing and presentation, and neuroactive ligand-receptor interaction, respectively.

摘要

目的

对微小RNA(miRNA)靶点进行系统追踪仍然是一项挑战。在我们的研究中,我们旨在通过整合miRNA过表达信息和序列数据,利用TargetScore来研究miRNA203和miRNA - 146a在银屑病中的潜在靶点,并进一步揭示miRNA203和miRNA - 146a在银屑病中的功能。

方法

这是一项利用已发表的银屑病微阵列数据进行的病例对照生物信息学分析。我们通过结合从TargetScan上下文评分获得的对数变化倍数和序列评分、保守靶向概率来计算TargetScore,并得出TargetScore的分布。根据未经验证和已验证靶点的不同TargetScore分布选择评分阈值。基于TargetScore阈值预测miRNA - 203和miRNA - 146a的潜在靶基因。为了揭示miRNA - 203和miRNA - 146a的功能,我们对miRNA - 203和miRNA - 146a的靶点进行了通路富集分析。

结果

选择TargetScore >0.4作为阈值来筛选可信度较低的靶点,因为我们观察到在TargetScore = 0.4时两种分布之间几乎没有重叠。基于TargetScore >0.4,鉴定出miRNA - 203的49个靶基因和miRNA - 146a的17个靶基因。通路富集结果表明,miRNA - 203的靶基因(包括KIR2DL1、HLA - DQA1、KIR3DL1)仅参与抗原加工和呈递。miRNA - 146a的靶基因(包括ADORA3、CYSLTR2、HRH4)仅参与神经活性配体 - 受体相互作用。

结论

MiRNA203和miRNA - 146a在银屑病进展中发挥重要作用,分别部分通过调节抗原加工和呈递以及神经活性配体 - 受体相互作用的通路来实现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7cf/6203501/e22d60c46ef4/medi-97-e12671-g003.jpg

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