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Correlation analyses revealed global microRNA–mRNA expression associations in human peripheral blood mononuclear cells

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Abstract

MicroRNAs (miRNAs) can regulate gene expression through binding to complementary sites in the 3′-untranslated regions of target mRNAs, which will lead to existence of correlation in expression between miRNA and mRNA. However, the miRNA–mRNA correlation patterns are complex and remain largely unclear yet. To establish the global correlation patterns in human peripheral blood mononuclear cells (PBMCs), multiple miRNA–mRNA correlation analyses and expression quantitative trait locus (eQTL) analysis were conducted in this study. We predicted and achieved 861 miRNA–mRNA pairs (65 miRNAs, 412 mRNAs) using multiple bioinformatics programs, and found global negative miRNA–mRNA correlations in PBMC from all 46 study subjects. Among the 861 pairs of correlations, 19.5% were significant (P < 0.05) and ~70% were negative. The correlation network was complex and highlighted key miRNAs/genes in PBMC. Some miRNAs, such as hsa-miR-29a, hsa-miR-148a, regulate a cluster of target genes. Some genes, e.g., TNRC6A, are regulated by multiple miRNAs. The identified genes tend to be enriched in molecular functions of DNA and RNA binding, and biological processes such as protein transport, regulation of translation and chromatin modification. The results provided a global view of the miRNA–mRNA expression correlation profile in human PBMCs, which would facilitate in-depth investigation of biological functions of key miRNAs/mRNAs and better understanding of the pathogenesis underlying PBMC-related diseases.

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Acknowledgements

The study was supported by National Natural Science Foundation of China (81473046, 31071097, 31271336, 81372024, 81373010, 81502868, 31401079, 81401343, 81541068), the Natural Science Foundation of Jiangsu Province (BK20130300, BK20150346), the Natural Science Research Project of Jiangsu Provincial Higher Education (16KJA330001), the Startup Fund from Soochow University (Q413900112, Q413900712), and a Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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    Authors and Affiliations

    1. Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou, 215123, Jiangsu, People’s Republic of China

      Lan Wang, Fei-Yan Deng, Long-Fei Wu, Xing-Bo Mo, Xiao-Wei Zhu, Wei Xia, Fang-Fei Xie, Pei He, Peng-Fei Bing, Ying-Hua Qiu, Xiang Lin, Xin Lu, Lei Zhang & Shu-Feng Lei

    2. Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, People’s Republic of China

      Lan Wang, Fei-Yan Deng, Long-Fei Wu, Xing-Bo Mo, Xiao-Wei Zhu, Wei Xia, Fang-Fei Xie, Pei He, Peng-Fei Bing, Ying-Hua Qiu, Xiang Lin, Xin Lu, Lei Zhang, Yong-Hong Zhang & Shu-Feng Lei

    3. The Second Affiliated Hospital of Soochow University, Suzhou, 215008, Jiangsu, People’s Republic of China

      Jiang Zhu

    4. Center for Disease Prevention and Control, Yichun, 336000, Jiangxi, People’s Republic of China

      Lan Wang

    5. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

      Neng-Jun Yi

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    1. Lan Wang
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    Correspondence to Shu-Feng Lei.

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    Funding

    This study was funded by National Natural Science Foundation of China (81473046, 31071097, 31271336, 81372024, 81373010, 81502868, 31401079, 81401343, 81541068), the Natural Science Foundation of Jiangsu Province (BK20130300, BK20150346), the Project funded by China Postdoctoral Science Foundation (2014M551649), the Natural Science Research Project of Jiangsu Provincial Higher Education (16KJA330001), the Startup Fund from Soochow University (Q413900112, Q413900712), and a Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions.

    Conflict of interest

    All authors declare that they have no conflict of interest.

    Ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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    Informed consent was obtained from all individual participants included in the study.

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    All data generated or analyzed during this study are included in this published article and its supplementary information files.

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    Communicated by S. Hohmann.

    Lan Wang and Jiang Zhu contributed equally to this article.

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    438_2017_1367_MOESM1_ESM.tif

    Supplementary material 1: Fig. S1 The physical distance from miRNA to mRNA transcript start site against P value from the eQTL analysis. The x-axis is physical distance in kb between transcript start site of miRNA and its target mRNA. The y-axis is -lgP of miRNA-eQTL. The P-values were generated from regression analyses, in which the confounding effects of age and disease activity on mRNA expression have been adjusted (TIFF 4704 kb)

    Supplementary material 2 (XLSX 12 kb)

    Supplementary material 3 (XLSX 64 kb)

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    Supplementary material 5 (XLSX 12 kb)

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    Wang, L., Zhu, J., Deng, FY. et al. Correlation analyses revealed global microRNA–mRNA expression associations in human peripheral blood mononuclear cells. Mol Genet Genomics 293, 95–105 (2018). https://doi.org/10.1007/s00438-017-1367-4

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