SP1-induced lncRNA TUG1 regulates proliferation and apoptosis in islet cells of type 2 diabetes mellitus via the miR-188-3p/FGF5 axis

P. Zhang, Y.-N. Li, S. Tu, X.-B. Cheng

Department of Endocrinology, the First Affiliated Hospital of Soochow University, Suzhou, China. 20174132030@stu.suda.edu.cn

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• Metabolism

OBJECTIVE: To elucidate the role of TUG1 in the onset of type 2 diabetes mellitus (T2DM) and the potential mechanism.

MATERIALS AND METHODS: Relative levels of TUG1 and SP1 in high-fat diet animal model and high-glucose cell model were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and their correlation was analyzed. Potential binding sites in the promoter sequences of TUG1 and SP1 were predicted using the JASPAR. Their interaction was further confirmed by chromatin immunoprecipitation (ChIP) and Dual-Luciferase reporter assay. The influences of TUG1 on proliferative and apoptotic potentials in Min6 cells were examined by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2’-deoxyuridine (EdU) assay and flow cytometry, respectively. Subsequently, the interaction in the TUG1/miR-188-3p /FGF5 axis was similarly explored by Dual-Luciferase reporter assay.

RESULTS: SP1 and TUG1 were downregulated in high-fat and high-glucose models, and they displayed a positive correlation. TUG1 bound E2 region in SP1 promoters. Knockdown of TUG1 inhibited proliferative rate and induced apoptosis in high-glucose-treated Min6 cells. Furthermore, the TUG1 / miR-188-3p /FGF5 axis was identified to be responsible for regulating Min6 cell functions.

CONCLUSIONS: SP1 induces TUG1 downregulation in T2DM cell models, which further regulates proliferative and apoptotic potentials in islet cells by activating the miR-188-3p/FGF5 axis.

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