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MicroRNA‑18 promotes apoptosis of islet β‑cells via targeting NAV1

  • Authors:
    • Honghua Fei
    • Mingyan Shi
    • Lianhong Chen
    • Zhe Wang
    • Lihua Suo
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China, Department of Blood Transfusion, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China
    Copyright: © Fei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 389-396
    |
    Published online on: April 24, 2019
       https://doi.org/10.3892/etm.2019.7527
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Abstract

The detailed pathogenesis of diabetes mellitus (DM) remains to be fully elucidated. The purpose of the present study was to explore the role of microRNA (miR)‑18 in DM and its underlying mechanisms, providing novel ideas for the treatment of the disease. After inflammatory factor‑mediated induction, miR‑18 expression in the islet β‑cell line MIN6 was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). miR‑18 mimics and miR‑18 inhibitor were then constructed and transfected into MIN6 cells. The mRNA levels of pro‑insulin in MIN6 cells were also detected by RT‑qPCR. Released insulin levels and insulin secretion function of MIN6 cells were accessed by ELISA and glucose‑stimulated insulin secretion assay, respectively. Apoptosis of MIN6 cells was detected by a terminal deoxynucleotidyl transferase‑mediated deoxyuridinetriphosphate nick end labeling assay and western blot analysis of apoptotic proteins. The binding interaction of miR‑18 and neuron navigator 1(NAV1), a constituent of the phosphoinositide 3‑kinase (PI3K)/AKT pathway, was assessed using a dual‑luciferase reporter gene assay. Finally, the regulatory effect of miR‑18 on the PI3K/AKT pathway was determined by western blot analysis. After induction of inflammatory factors in MIN6 cells, miR‑18 expression was markedly upregulated. Transfection with miR‑18 mimics inhibited pro‑insulin levels, as well as insulin production and secretion capacity. miR‑18 knockdown partially abrogated the inhibited insulin secretion capacity induced by interleukin‑1β (IL‑1β) treatment. In addition, apoptosis of MIN6 cells was increased by miR‑18 mimics. The dual‑luciferase reporter gene assay confirmed the direct binding of miR‑18 to NAV1. Western blot analysis suggested that miR‑18 markedly inhibited the PI3K/AKT pathway in MIN6 cells. In conclusion, miR‑18 expression is upregulated by IL‑1β induction in islet β‑cells. It was demonstrated that miR‑18 promotes apoptosis of islet β‑cells at least partially by inhibiting NAV1 expression and insulin production via suppression of the PI3K/AKT pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Fei H, Shi M, Chen L, Wang Z and Suo L: MicroRNA‑18 promotes apoptosis of islet β‑cells via targeting NAV1. Exp Ther Med 18: 389-396, 2019.
APA
Fei, H., Shi, M., Chen, L., Wang, Z., & Suo, L. (2019). MicroRNA‑18 promotes apoptosis of islet β‑cells via targeting NAV1. Experimental and Therapeutic Medicine, 18, 389-396. https://doi.org/10.3892/etm.2019.7527
MLA
Fei, H., Shi, M., Chen, L., Wang, Z., Suo, L."MicroRNA‑18 promotes apoptosis of islet β‑cells via targeting NAV1". Experimental and Therapeutic Medicine 18.1 (2019): 389-396.
Chicago
Fei, H., Shi, M., Chen, L., Wang, Z., Suo, L."MicroRNA‑18 promotes apoptosis of islet β‑cells via targeting NAV1". Experimental and Therapeutic Medicine 18, no. 1 (2019): 389-396. https://doi.org/10.3892/etm.2019.7527
Copy and paste a formatted citation
x
Spandidos Publications style
Fei H, Shi M, Chen L, Wang Z and Suo L: MicroRNA‑18 promotes apoptosis of islet β‑cells via targeting NAV1. Exp Ther Med 18: 389-396, 2019.
APA
Fei, H., Shi, M., Chen, L., Wang, Z., & Suo, L. (2019). MicroRNA‑18 promotes apoptosis of islet β‑cells via targeting NAV1. Experimental and Therapeutic Medicine, 18, 389-396. https://doi.org/10.3892/etm.2019.7527
MLA
Fei, H., Shi, M., Chen, L., Wang, Z., Suo, L."MicroRNA‑18 promotes apoptosis of islet β‑cells via targeting NAV1". Experimental and Therapeutic Medicine 18.1 (2019): 389-396.
Chicago
Fei, H., Shi, M., Chen, L., Wang, Z., Suo, L."MicroRNA‑18 promotes apoptosis of islet β‑cells via targeting NAV1". Experimental and Therapeutic Medicine 18, no. 1 (2019): 389-396. https://doi.org/10.3892/etm.2019.7527
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