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MicroRNA‑143‑3p levels are reduced in the peripheral blood of patients with gestational diabetes mellitus and influences pancreatic β‑cell function and viability

  • Authors:
    • Cairu Liu
    • Haiqin Feng
    • Lina Zhang
    • Yiran Guo
    • Jinjin Ma
    • Liping Yang

  • View Affiliations

  • Published online on: December 30, 2022     https://doi.org/10.3892/etm.2022.11780
  • Article Number: 81

  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pancreatic β‑cell dysfunction has been demonstrated to mediate key roles in the pathogenesis of gestational diabetes mellitus (GDM). Accumulating evidence has supported the functional involvement of microRNAs (miRNAs) in various types of diabetes, including GDM. However, the detailed biological effect of miRNAs in pancreatic β‑cell dysfunction remains poorly understood. In the present study, microarray data of miRNAs in the blood plasma of patients with GDM were retrieved from the Gene Expression Omnibus dataset under the accession number GSE98043. Reverse transcription‑quantitative PCR (RT‑qPCR) was performed to measure the expression levels of miR‑143‑3p in the blood plasma isolated from 30 female patients with GDM women and 30 healthy female individuals. Subsequently, murine pancreatic β‑cell line, MIN6 cells were treated with high glucose (HG) to construct in vitro cell models of GDM. miR‑143‑3p in HG‑treated MIN6 cells was overexpressed or knocked down using miR‑143‑3p mimics and miR‑143‑3p inhibitor. Cell viability, insulin secretion and proinflammatory cytokine production were examined using CCK‑8 and ELISA, respectively Cell apoptosis was measured by flow cytometry assay. The protein expression levels of proteins involved in the TAK1/NF‑κB pathway were also assessed using western blot. The levels of miR‑143‑3p were found to be markedly lower in samples from patients with GDM, which were in turn negatively correlated with blood glucose levels. Overexpression of miR‑143‑3p in MIN6 cells significantly reversed HG‑induced cell apoptosis and impairments in cell viability and insulin secretion. In addition, miR‑143‑3p overexpression attenuated HG‑induced proinflammatory cytokine production by MIN6 cells. Subsequently, TGFβ‑activated kinase 1 (TAK1), an upstream regulator of the NF‑κB pathway, was found to be a direct target of miR‑143‑3p in pancreatic β cells through luciferase assays and western blot. Overexpression of TAK1 was revealed to abolish the curative effects of miR‑143‑3p on insulin secretion, cell viability and inflammatory response in HG‑treated MIN6 cells. In addition, miR‑143‑3p could inactivate the NF‑κB pathway by inhibiting TAK1 expression. Collectively, these results suggest that miR‑143‑3p levels are downregulated in the peripheral blood of patients with GDM. Therefore, miR‑143‑3p overexpression may serve as a method for preventing pancreatic β cell dysfunction by inhibiting the TAK1/NF‑κB pathway.
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February-2023
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Spandidos Publications style
Liu C, Feng H, Zhang L, Guo Y, Ma J and Yang L: MicroRNA‑143‑3p levels are reduced in the peripheral blood of patients with gestational diabetes mellitus and influences pancreatic β‑cell function and viability. Exp Ther Med 25: 81, 2023
APA
Liu, C., Feng, H., Zhang, L., Guo, Y., Ma, J., & Yang, L. (2023). MicroRNA‑143‑3p levels are reduced in the peripheral blood of patients with gestational diabetes mellitus and influences pancreatic β‑cell function and viability. Experimental and Therapeutic Medicine, 25, 81. https://doi.org/10.3892/etm.2022.11780
MLA
Liu, C., Feng, H., Zhang, L., Guo, Y., Ma, J., Yang, L."MicroRNA‑143‑3p levels are reduced in the peripheral blood of patients with gestational diabetes mellitus and influences pancreatic β‑cell function and viability". Experimental and Therapeutic Medicine 25.2 (2023): 81.
Chicago
Liu, C., Feng, H., Zhang, L., Guo, Y., Ma, J., Yang, L."MicroRNA‑143‑3p levels are reduced in the peripheral blood of patients with gestational diabetes mellitus and influences pancreatic β‑cell function and viability". Experimental and Therapeutic Medicine 25, no. 2 (2023): 81. https://doi.org/10.3892/etm.2022.11780