Rbfox-1 contributes to CaMKIIα expression and intracerebral hemorrhage-induced secondary brain injury via blocking micro-RNA-124

J Cereb Blood Flow Metab. 2021 Mar;41(3):530-545. doi: 10.1177/0271678X20916860. Epub 2020 Apr 4.


RNA-binding protein fox-1 homolog 1 (Rbfox-1), an RNA-binding protein in neurons, is thought to be associated with many neurological diseases. To date, the mechanism on which Rbfox-1 worsens secondary cell death in ICH remains poorly understood. In this study, we aimed to explore the role of Rbfox-1 in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) and to identify its underlying mechanisms. We found that the expression of Rbfox-1 in neurons was significantly increased after ICH, which was accompanied by increases in the binding of Rbfox-1 to Ca2+/calmodulin-dependent protein kinase II (CaMKIIα) mRNA and the protein level of CaMKIIα. In addition, when exposed to exogenous upregulation or downregulation of Rbfox-1, the protein level of CaMKIIα showed a concomitant trend in brain tissue, which further suggested that CaMKIIα is a downstream-target protein of Rbfox-1. The upregulation of both proteins caused intracellular-Ca2+ overload and neuronal degeneration, which exacerbated brain damage. Furthermore, we found that Rbfox-1 promoted the expression of CaMKIIα via blocking the binding of micro-RNA-124 to CaMKIIα mRNA. Thus, Rbfox-1 is expected to be a promising therapeutic target for SBI after ICH.

Keywords: CaMKIIα; Rbfox-1; intracerebral hemorrhage; micro-RNA-124; secondary brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antagomirs / metabolism
  • Apoptosis / drug effects
  • Behavior, Animal
  • Brain / metabolism
  • Brain / pathology
  • Brain Injuries / etiology
  • Brain Injuries / metabolism
  • Brain Injuries / pathology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cells, Cultured
  • Cognitive Dysfunction / etiology
  • Disease Models, Animal
  • Intracranial Hemorrhages / chemically induced
  • Intracranial Hemorrhages / complications*
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neurons / cytology
  • Neurons / metabolism
  • Oxyhemoglobins / pharmacology
  • RNA Interference
  • RNA Splicing Factors / antagonists & inhibitors
  • RNA Splicing Factors / genetics
  • RNA Splicing Factors / metabolism*
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley


  • Antagomirs
  • MIRN124 microRNA, rat
  • MicroRNAs
  • Oxyhemoglobins
  • RNA Splicing Factors
  • RNA, Small Interfering
  • RbFox-1 protein, rat
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2