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Comprehensive Analysis of lncRNA and miRNA Expression Profiles and ceRNA Network Construction in Osteoporosis

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Abstract

Multiple profiling studies have identified a number of non-coding RNAs associated with the pathogenesis of human diseases. However, the exact regulatory mechanisms and functions of these non-coding RNAs in the development of osteoporosis have not yet been explored. Transcriptome gene expression and miRNA microarray data from peripheral blood monocytes of five high hip bone mineral density (BMD) subjects and five low hip BMD subjects were analyzed. Differentially expressed mRNAs, lncRNAs, and miRNAs were identified and subjected to functional enrichment analysis. Additionally, protein–protein interaction (PPI), lncRNA–mRNA, and mRNA–lncRNA–miRNA competing endogenous RNA (ceRNA) networks were constructed. Differential analysis revealed that 297 mRNAs, 151 lncRNAs, and 38 miRNAs were significantly differentially expressed between peripheral blood monocytes from high and low hip BMD subjects. Key genes including ACLY, HSPA5, and AKT1 were subsequently identified in the PPI network. Additionally, differentially expressed lncRNAs were primarily enriched in the citrate cycle (TCA cycle), biosynthesis of antibiotics, and carbon metabolism pathways. Finally, the mRNA–lncRNA–miRNA network revealed several key ceRNA regulatory relationships among the transcripts and non-coding RNAs. Key mRNAs and non-coding RNAs identified in the networks represent potential biomarkers or targets in the diagnosis and management of osteoporosis. Our findings represent a resource for further functional research on the ceRNA regulation mechanism of non-coding RNA in osteoporosis.

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Data Availability

The datasets analyzed in the present study are available from the Gene Expression Omnibus repository, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE35959.

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Acknowledgements

We thank Mr. Donglin Cheng for his technical assistance.

Funding

This study is supported by the Fundamental Research Funds for the Central Universities (Grant No. WK9110000093) and National Natural Science Foundation of China (Grant No. 81902201).

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Authors and Affiliations

  1. Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China

    Xianzuo Zhang, Guoyuan Li & Xifu Shang

  2. CAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of China, Hefei, 230026, Anhui, China

    Haiyi Liang

  3. IAT-Chungu Joint Laboratory for Additive Manufacturing, Anhui Chungu 3D Printing Institute of Intelligent Equipment and Industrial Technology, Wuhu, 241200, Anhui, China

    Haiyi Liang

  4. Department of Medical Physics, School of Health Sciences, University of Ioannina, 45110, Ioannina, Greece

    Nikolaos Kourkoumelis

  5. School of Biotechnology, Jiangnan University, Wuxi, 214122, Jiangsu, China

    Zhaodong Wu

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  1. Xianzuo Zhang
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Contributions

XFS conceived the idea and designed the project. NK performed the data analysis. XZZ and ZDW wrote the paper. HYL and GYL revised the manuscript. All authors have read and approved the manuscript.

Corresponding authors

Correspondence to Guoyuan Li or Xifu Shang.

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Conflict of interest

Xianzuo Zhang, Haiyi Liang, Nikolaos Kourkoumelis, Zhaodong Wu, and Guoyuan Li and Xifu Shang declare that they have no conflict of interest.

Human and Animal Rights

The study was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments. The study protocol has been approved by the Institutional Review Boards of The First Affiliated Hospital of USTC (University of Science and Technology of China).

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223_2019_643_MOESM1_ESM.jpg

Supplementary Figure 1 The mRNA-lncRNA-miRNA pathway network. Green circular nodes represent mRNAs, green triangular nodes represent lncRNAs, red rectangular nodes represent miRNAs, and grey arrows represent pathways. Supplementary file1 (JPG 509 kb)

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Zhang, X., Liang, H., Kourkoumelis, N. et al. Comprehensive Analysis of lncRNA and miRNA Expression Profiles and ceRNA Network Construction in Osteoporosis. Calcif Tissue Int 106, 343–354 (2020). https://doi.org/10.1007/s00223-019-00643-9

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  • DOI: https://doi.org/10.1007/s00223-019-00643-9

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