MiR-let-7d-3p regulates IL-17 expression through targeting AKT1/mTOR signaling in CD4+ T cells
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The aberrant expression of interleukin-17 (IL-17) has been reported in the pathogenesis of autoimmune diseases, such as primary Sjögren’s syndrome (pSS). However, the detailed mechanism remains poorly understood. We aim to characterize the expression of IL-17 in pSS and analyze the detailed underlying mechanism. IL-17 and microRNA miR-let-7d-3p expression were assayed by quantitative real-time PCR and Western blot, and proliferation-related protein expression was measured by Western blot. Luciferase reporter assays were performed to detect the direct regulation of IL-17 by miR-let-7d-3p. Expression of miR-let-7d-3p was negatively correlated with the expression of IL-17 in patients with pSS. Besides, the AKT1/mTOR signaling pathway was found critical for miR-let-7d-3p-mediated IL-17 expression. Furthermore, miR-let-7d-3p targeted AKT1 to bridge the regulation of IL-17. Finally, we verified AKT1 co-expression could rescue IL-17 downregulation caused by miR-let-7d-3p. Our study revealed novel mechanism that how did IL-17 was exactly modulated by miR-let-7d-3p and the potential of miR-let-7d-3p-AKT1-mTOR-IL-17 signaling as therapeutic targets for autoimmune diseases.
KeywordsInterleukin-17 Primary Sjögren’s syndrome miR-let-7d-3p AKT1 mTOR
We thank the Affiliated Hospital to Bengbu Medical college for the capital and equipment support.
Jian Wang, Xin Wang, and Longfei Wang performed the experiments. Jian Wang, Xin Wang, and Zhijun Li analyzed data. Longfei Wang, Chao Sun, Changhao Xie, and Zhijun Li contributed reagents/materials/analysis tools. Jian Wang, Xin Wang, and Zhijun Li wrote the manuscript. All authors discussed the results and commented on the manuscript.
This work was supported by the Nature Science Key Program of Bengbu Medical College (no. BYKY1852ZD).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
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