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Xuezhen Zhang 1 Article
Basic Research
Long Non-Coding RNA TUG1 Attenuates Insulin Resistance in Mice with Gestational Diabetes Mellitus via Regulation of the MicroRNA-328-3p/SREBP-2/ERK Axis
Xuwen Tang, Qingxin Qin, Wenjing Xu, Xuezhen Zhang
Diabetes Metab J. 2023;47(2):267-286.   Published online January 19, 2023
DOI: https://doi.org/10.4093/dmj.2021.0216
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Long non-coding RNAs (lncRNAs) have been illustrated to contribute to the development of gestational diabetes mellitus (GDM). In the present study, we aimed to elucidate how lncRNA taurine upregulated gene 1 (TUG1) influences insulin resistance (IR) in a high-fat diet (HFD)-induced mouse model of GDM.
Methods
We initially developed a mouse model of HFD-induced GDM, from which islet tissues were collected for RNA and protein extraction. Interactions among lncRNA TUG1/microRNA (miR)-328-3p/sterol regulatory element binding protein 2 (SREBP-2) were assessed by dual-luciferase reporter assay. Fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), HOMA pancreatic β-cell function (HOMA-β), insulin sensitivity index for oral glucose tolerance tests (ISOGTT) and insulinogenic index (IGI) levels in mouse serum were measured through conducting gain- and loss-of-function experiments.
Results
Abundant expression of miR-328 and deficient expression of lncRNA TUG1 and SREBP-2 were characterized in the islet tissues of mice with HFD-induced GDM. LncRNA TUG1 competitively bound to miR-328-3p, which specifically targeted SREBP-2. Either depletion of miR-328-3p or restoration of lncRNA TUG1 and SREBP-2 reduced the FBG, FINS, HOMA-β, and HOMA-IR levels while increasing ISOGTT and IGI levels, promoting the expression of the extracellular signal-regulated kinase (ERK) signaling pathway-related genes, and inhibiting apoptosis of islet cells in GDM mice. Upregulation miR-328-3p reversed the alleviative effects of SREBP-2 and lncRNA TUG1 on IR.
Conclusion
Our study provides evidence that the lncRNA TUG1 may prevent IR following GDM through competitively binding to miR-328-3p and promoting the SREBP-2-mediated ERK signaling pathway inactivation.

Citations

Citations to this article as recorded by  
  • Diabetes and diabetic associative diseases: An overview of epigenetic regulations of TUG1
    Mohammed Ageeli Hakami
    Saudi Journal of Biological Sciences.2024; 31(5): 103976.     CrossRef
  • Effect of Tinospora cordifolia on gestational diabetes mellitus and its complications
    Ritu Rani, Havagiray Chitme, Avinash Kumar Sharma
    Women & Health.2023; 63(5): 359.     CrossRef
  • Therapeutic Effect of Tinospora cordifolia (Willd) Extracts on Letrozole-Induced Polycystic Ovarian Syndrome and its Complications in Murine Model
    Ritu Rani, Avinash Kumar Sharma, Havagiray R Chitme
    Clinical Medicine Insights: Endocrinology and Diabetes.2023;[Epub]     CrossRef
  • The role of ncRNA regulatory mechanisms in diseases—case on gestational diabetes
    Dong Gao, Liping Ren, Yu-Duo Hao, Nalini Schaduangrat, Xiao-Wei Liu, Shi-Shi Yuan, Yu-He Yang, Yan Wang, Watshara Shoombuatong, Hui Ding
    Briefings in Bioinformatics.2023;[Epub]     CrossRef
  • lncRNA TUG1 as Potential Novel Biomarker for Prognosis of Cardiovascular Diseases
    Habib Haybar, Narjes Sadat Sadati, Daryush Purrahman, Mohammad Reza Mahmoudian-Sani, Najmaldin Saki
    Epigenomics.2023; 15(23): 1273.     CrossRef

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