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miR-1290 promotes IL-8-mediated vascular endothelial cell adhesion by targeting GSK-3β

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Abstract

Background

MicroRNA-1290 (miR-1290) has been reported to be involved in many diseases and play a key role during the development process. However, the role of miR-1290 in atherosclerosis (AS) is still unclear.

Methods and results

The current study showed that the expressions of miR-1290 were high in serum of patients with hyperlipidemia. The functional role of miR-1290 were then investigated in human umbilical vein endothelial cells (HUVECs). Here, we found that miR-1290 expressions were notably enhanced in HUVECs mediated by IL-8. miR-1290 inhibitor repressed monocytic THP-1 cells adhesion to HUVECs by regulating ICAM-1 and VCAM-1, inhibited proliferation through regulating cyclinD1 and PCNA, and inhibited inflammatory response by regulating IL-1β. Mechanistically, we verified that miR-1290 mimic was able to directly target the 3′-UTR of GSK-3β mRNA using luciferase reporter assay. Knockdown of GSK-3β (si-GSK-3β) promoted HUVECs adhesion and the expression of IL-1β, and partially restore the depression effect of miR-1290 inhibitor on HUVECs adhesion and inflammation. In contrast, si-GSK-3β inhibited the proliferation of HUVECs and the expression of cyclinD1 and PCNA.

Conclusions

In summary, our study revealed that miR-1290 promotes IL-8-mediated the adhesion of HUVECs by targeting GSK-3β. However, GSK-3β is not the target protein for miR-1290 to regulate the proliferation of HUVECs. Our findings may provide potential target in atherosclerosis treatment.

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Funding

This work was supported by Liaoning Provincial Program for Top Discipline of Basic Medical Sciences, the National Natural Science Foundation of China (31370800, 81402916, 31070719, 30470394), the Educational Department of Liaoning Province (20072166, 2009A195, 2013023015) and Liaoning Provincial Program for Top Discipline of Basic Medical Sciences.

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Authors and Affiliations

Authors

Contributions

X.HX performed the experiments, analysed the data and wrote the paper. C.Y wrote the paper. L.XW and Z.X performed the experiments and analysed the data. L.JQ performed the experiments. H.XX, G.FH, H.XY and L.M analysed the data. W.XQ revised the paper. G.Y designed and wrote the paper. Z.Y designed and supervised research and revised the paper. All authors have read and approved the manuscript.

Corresponding authors

Correspondence to Ying Gao or Ying Zhao.

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Conflict of interest

All the authors confirm that there are no conflicts of interest.

Ethical approval

Written informed consent was obtained from all of the patients and the study were approved by the Ethics Committee of Dalian Central Hospital. All animal experiments were approved by the local research ethics review board of the Animal Ethics Committee of Dalian Medical University.

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Xu, H., Cui, Y., Liu, X. et al. miR-1290 promotes IL-8-mediated vascular endothelial cell adhesion by targeting GSK-3β. Mol Biol Rep 49, 1871–1882 (2022). https://doi.org/10.1007/s11033-021-06998-3

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  • DOI: https://doi.org/10.1007/s11033-021-06998-3

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