Overexpression of circARF3 mitigates TNF-α-induced inflammatory damage by up-regulating miR-125b

Cell Cycle. 2020 Jun;19(11):1253-1264. doi: 10.1080/15384101.2020.1731652. Epub 2020 Apr 24.

Abstract

Encephalitis is the highest disability illness. We studied the function and mechanisms of circular RNA circARF3 (circARF3) in neurocyte cell inflammatory damage. CCK-8 assay and flow cytometry were, respectively, employed for examining the influences of tumor necrosis factor α (TNF-α), circARF3 and microRNA (miR)-125b on cell viability and apoptosis. The expression of circARF3 and miR-125b were changed by employing cell transfection and the results were determined by using qRT-PCR. Besides, the expression of Bcl-2, Bax, Cleaved-caspase-3, interleukin (IL)-1β, IL-6, IL-8 and cell pathways-related proteins were examined by using Western blot. The productions of IL-6, IL-8 and IL-1β were also tested by ELISA. The level of reactive oxygen species (ROS) was examined by ROS assay. We found that TNF-α caused inflammatory damage showing as suppressed cell viability, enhanced cell apoptosis, and increased cytokines production and ROS generation. Besides, TNF-α inducement also markedly reduced circARF3 expression. circARF3 overexpression mitigated TNF-α-induced cell inflammatory damage. Moreover, miR-125b was targeted and positively regulated by circARF3. Furthermore, miR-125b inhibition could reverse the influences of circARF3 overexpression. Besides, circARF3 restrained the JNK and NF-κB pathways by up-regulation of miR-125b. In conclusion, overexpression of circARF3 mitigated cell inflammatory damage via inactivation of JNK and NF-κB pathways and thereby up-regulation of miR-125b.

Keywords: Encephalitis; TNF-α; circARF3; inflammation; miR-125b.

Publication types

  • Retracted Publication

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Humans
  • Inflammation / genetics*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / genetics
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • NF-kappa B / metabolism
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Tumor Necrosis Factor-alpha / adverse effects*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics*

Substances

  • MIRN125 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • RNA, Circular
  • Tumor Necrosis Factor-alpha