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Differentially expressed microRNAs in the corpus cavernosum from a murine model with type 2 diabetes mellitus-associated erectile dysfunction

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Abstract

To better understand the molecular aetiology of type 2 diabetes mellitus-associated erectile dysfunction (T2DMED) and to provide candidates for further study of its diagnosis and treatment, this study was designed to investigate differentially expressed microRNAs (miRNAs) in the corpus cavernosum (CC) of mice with T2DMED using GeneChip array techniques (Affymetrix miRNA 4.0 Array) and to predict target genes and signalling pathways regulated by these miRNAs based on bioinformatic analysis using TargetScan, the DAIAN web platform and DAVID. In the initial screening, 21 miRNAs appeared distinctly expressed in the T2DMED group (fold change ≥3, p ≤ 0.01). Among them, the differential expression of miR-18a, miR-206, miR-122, and miR-133 were confirmed by qRT-PCR (p < 0.05 and FDR <5 %). According to bioinformatic analysis, the four miRNAs were speculated to play potential roles in the mechanisms of T2DMED via regulating 28 different genes and several pathways, including apoptosis, fibrosis, eNOS/cGMP/PKG, and vascular smooth muscle contraction processes, which mainly focused on influencing the functions of the endothelium and smooth muscle in the CC. IGF-1, as one of the target genes, was verified to decrease in the CCs of T2DMED animals via ELISA and was confirmed as the target of miR-18a or miR-206 via luciferase assay. Finally, these four miRNAs deserve further confirmation as biomarkers of T2DMED in larger studies. Additionally, miR-18a and/or miR-206 may provide new preventive/therapeutic targets for ED management by targeting IGF-1.

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Authors and Affiliations

  1. State Key Laboratory of Reproductive Medicine, Department of Andrology, Maternity Hospital Affiliated to Nanjing Medical University, Nanjing, China

    Feng Pan, Jinwei You, Jiehua Ma, Lianjun Pan & Aixia Zhang

  2. Department of Comparative Medicine, Jinling Hospital, School of Clinical Medicine, Nanjing University, Nanjing, China

    Jinwei You

  3. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, Nanjing University, Nanjing, China

    Feng Pan, Yuan Liu & Qipeng Zhang

  4. Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China

    Xuefeng Qiu & Wen Yu

Authors
  1. Feng Pan
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  2. Jinwei You
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  3. Yuan Liu
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  4. Xuefeng Qiu
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  5. Wen Yu
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  6. Jiehua Ma
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  7. Lianjun Pan
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  8. Aixia Zhang
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  9. Qipeng Zhang
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Corresponding authors

Correspondence to Aixia Zhang or Qipeng Zhang.

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Funding

This study was funded by Natural Science Foundation of Jiangsu Province (BK20160138), Scientific Research Project of Maternity and Child Health and Reproductive Health of Family Planning, Jiangsu Province (F201530), Key Project supported by Science and Technology development Foundation, Nanjing Medical University (2014NJMUZD053), and Nanjing science and technology project (201402024).

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed.

Additional information

Communicated by S. Hohmann.

F. Pan and J. You consider that the first two authors should be regarded as joint first authors.

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Pan, F., You, J., Liu, Y. et al. Differentially expressed microRNAs in the corpus cavernosum from a murine model with type 2 diabetes mellitus-associated erectile dysfunction. Mol Genet Genomics 291, 2215–2224 (2016). https://doi.org/10.1007/s00438-016-1250-8

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  • DOI: https://doi.org/10.1007/s00438-016-1250-8

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