MicroRNA-30b participates in the pathological process of hyperuricemia by regulating interleukin-6 receptor

Nucleosides Nucleotides Nucleic Acids. 2020;39(8):1162-1178. doi: 10.1080/15257770.2020.1780439. Epub 2020 Jul 9.

Abstract

The present study aimed to examine the expression of hyperuricemia (HUA)-related factors in the body fluids of HUA patients and in renal tissues and body fluids of HUA mice to elucidate the underlying mechanism of HUA and provide theoretical basis for the diagnosis, prevention and treatment of this disease. A total of 51 HUA patients (HUA group), and 36 healthy subjects (control group) were included in the present study. The peripheral blood and urine were collected from all patients and healthy subjects. A total of 20 male Kunming mice were used to construct HUA model, and another 20 mice were used as controls. The kidney tissues, peripheral blood and urine were collected from all mice. ELISA was performed to determine the levels of interleukin-6 receptor (IL-6R) proteins in the serum and urine of human or mice, while western blotting was employed to determine the protein expression in the kidney tissues of mice. Quantitative real-time polymerase chain reaction was used to measure the expression of mRNA and miR-30b in all sample types. Dual luciferase reporter assay was performed to identify the direct interaction between 3'-untranslated region of IL-6R mRNA and miR-30b. The expression of IL-6R mRNA and protein was increased in serum and urine of HUA patients, while the expression of miR-30b was reduced in HUA patients when compared with healthy subjects. The contents of uric acid, urea nitrogen and creatinine in the blood of HUA mice model were significantly elevated. Similarly, the expression of IL-6R mRNA and protein was increased in kidney, serum and urine of HUA mice model, while the expression of miR-30b was reduced in kidney tissues, serum and urine of HUA mice model. Dual luciferase reporter assay showed that miR-30b was able to bind with 3'-UTR seed region of IL-6R mRNA to regulate its expression. These findings demonstrated that the expression of IL-6R in patients and mouse with HUA is elevated, which is related with the down-regulation of miR-30b. Therefore, miR-30b might participate in the pathological process of HUA by regulating IL-6R.

Keywords: MicroRNA-30b; hyperuricemia; interleukin-6 receptor; pathological process.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Female
  • Humans
  • Hyperuricemia / metabolism*
  • Hyperuricemia / pathology
  • Male
  • Mice
  • Mice, Inbred Strains
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Receptors, Interleukin-6 / genetics
  • Receptors, Interleukin-6 / metabolism*

Substances

  • IL6R protein, human
  • Il6ra protein, mouse
  • MIRN30b microRNA, human
  • MIRN30b microRNA, mouse
  • MicroRNAs
  • Receptors, Interleukin-6