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

Hongxin Xu, Ying Cui, Xianwei Liu, Xiao Zheng, Jiaqing Liu, Xinxin Hu, Fuhua Gao, Xiaoyan Hu, Mei Li, Xiaoqing Wei, Ying Gao, Ying Zhao
Author Information
  1. Hongxin Xu: Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
  2. Ying Cui: Molecular Medical Laboratory, College of Basic Medical Science, Dalian Medical University, Dalian, China.
  3. Xianwei Liu: Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
  4. Xiao Zheng: Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
  5. Jiaqing Liu: Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
  6. Xinxin Hu: Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
  7. Fuhua Gao: Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
  8. Xiaoyan Hu: Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
  9. Mei Li: Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Dalian Medical University, Dalian, China.
  10. Xiaoqing Wei: Molecular Medical Laboratory, College of Basic Medical Science, Dalian Medical University, Dalian, China.
  11. Ying Gao: Liaoning Provincial Core Lab of Medical Molecular Biology, Dalian Medical University, Dalian, China. gaoying200018@126.com.
  12. Ying Zhao: Molecular Medical Laboratory, College of Basic Medical Science, Dalian Medical University, Dalian, China. zhaoying20001105@126.com.

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.

Keywords

References

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MeSH Term

Apoptosis
Cell Proliferation
Glycogen Synthase Kinase 3 beta
Human Umbilical Vein Endothelial Cells
Humans
Interleukin-8
MicroRNAs

Chemicals

CXCL8 protein, human
Interleukin-8
MIRN1290 microRNA, human
MicroRNAs
GSK3B protein, human
Glycogen Synthase Kinase 3 beta