The metabolic syndrome (MS) is a cluster of interrelated risk factors including diabetes mellitus, abdominal obesity, high cholesterol, and hypertension, which can significantly increase mortality and disability. Accumulating evidence suggest that long non-coding RNAs (lncRNAs) are involved in the pathogenesis of human metabolic diseases. However, little is known about the regulatory role of lncRNAs in MS. In this work, we proposed a method for identifying potential MS-associated lncRNAs by constructing an lncRNA–miRNA–mRNA network (LMMN). Firstly, we constructed LMMN by integrating MS-associated genes, miRNA–mRNA interactions, miRNA–lncRNA interactions and mRNA/miRNA expression profiles in patients with MS. Then, we predicted potential MS-associated lncRNAs based on the topological properties of LMMN. As a result, we identified XIST as the most important lncRNA in LMMN. Furthermore, we focused on XIST/miR-214-3p and mir-181a-5p/PTEN axis and validated their expression in MS using real-time quantitative polymerase chain reaction (RT-qPCR). The RT-qPCR results showed that the expression of XIST and PTEN was significantly decreased (P < 0.05) while the expression of miR-214-3p was significantly increased (P < 0.05) in peripheral blood mononuclear cells (PBMCs) of patients with MS, compared with healthy controls. In addition, correlation analysis showed that XIST was negatively correlated with serum C peptide and PTEN was positively correlated with BMI of MS patients. Our findings provided new evidence for further exploring the regulatory role of XIST and other lncRNAs in MS.
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Users can freely access MS-associated lncRNA–miRNA–mRNA network, XIST-centered lncRNA–miRNA–mRNA network and XIST–miRNA–PTEN network through the following link: http://www.ndexbio.org/#/networkset/df19b350-593a-11ea-bfdc-0ac135e8bacf?accesskey=771d8c38dc933a19f1ccbfb5b1c3c9105177b8170879bd4215c1d0a6ec62cd16.
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This work was supported by Innovation Talents Project of Harbin Science and Technology Bureau (2017RAQXJ027), the Natural Science Foundation of Heilongjiang Province (LH2019F023), the Fundamental Research Foundation for Universities of Heilongjiang Province (LGYC2018JQ003), and China Scholarship Council.
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Yao, D., Lin, Z., Zhan, X. et al. Identifying potential functional lncRNAs in metabolic syndrome by constructing a lncRNA–miRNA–mRNA network. J Hum Genet 65, 927–938 (2020). https://doi.org/10.1038/s10038-020-0753-7