Hsa_circ_0005050 interacts with ILF3 and affects cell apoptosis and proliferation by disrupting the balance between p53 and p65

Chem Biol Interact. 2022 Dec 1;368:110208. doi: 10.1016/j.cbi.2022.110208. Epub 2022 Oct 6.

Abstract

The regulatory network between arsenic, genes and signaling pathways has been reported in arsenic carcinogenesis. Studies on circRNA represent a growing field, but the extent to circRNA potential mechanisms remains poorly understood. So this study we explore the systematic function of hsa_circ_0005050 in mediating the cell apoptosis and proliferation. We demonstrated that hsa_circ_0005050 was highly expressed in subjects who are long-term exposed to arsenic, and could be induced by NaAs2O3 in A549 and 16HBE. Knockdown of hsa_circ_0005050 promotes A549 cell viability, whereas exerts the opposite effects in 16HBE. Mechanistically, hsa_circ_0005050 regulates the p53 and NF-κB signaling pathway involved in the apoptosis and proliferation. And we found that hsa_circ_0005050 could directly bind to the RNA binding protein ILF3 and mutually influence each other's formation. Upon si-hsa_circ_0005050, ILF3 export to the cytoplasm resulting the formation of a ternary complex ILF3-p65-IκBA, breaks the balance of p53 and NF-κB pathway and induces A549 apoptosis and leads to 16HBE proliferation. As a result of these investigations, suggestions were identified for future research.

Keywords: Arsenic; Cell apoptosis; Cell proliferation; NF-κB and P53 balance; circRNA-protein complex; hsa_circ_0005050.

MeSH terms

  • Apoptosis / genetics
  • Arsenic Poisoning
  • Arsenic*
  • Carcinogenesis / chemically induced
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • NF-kappa B / metabolism
  • Nuclear Factor 90 Proteins / genetics
  • Nuclear Factor 90 Proteins / metabolism
  • RNA, Circular / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Arsenic
  • ILF3 protein, human
  • NF-kappa B
  • Nuclear Factor 90 Proteins
  • RNA, Circular
  • Tumor Suppressor Protein p53