2. Academic Validation
  3. Hsa_circ_0049472 contributed to amyloid-beta peptide-induced neurotoxicity, apoptosis and inflammation via regulating PI3K-AKT signaling pathway by interacting with miR-22-3p/ZNF217 axis

Hsa_circ_0049472 contributed to amyloid-beta peptide-induced neurotoxicity, apoptosis and inflammation via regulating PI3K-AKT signaling pathway by interacting with miR-22-3p/ZNF217 axis

  • Brain Res Bull. 2024 Jun 7:215:111004. doi: 10.1016/j.brainresbull.2024.111004.
Yuanrun Xie 1,  Dan Xie 2,  Chao Chen 3
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, China.
  • 2 Department of Otolaryngology, Huangshi No.5 Hospital, Huangshi City, Hubei, China.
  • 3 Department of Neurosurgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, China. Electronic address: 15072036836@163.com.
PMID: 38852653 DOI: 10.1016/j.brainresbull.2024.111004
Abstract

Background: Circular RNAs (circRNAs) exhibited important roles in Alzheimer's disease (AD). Here, we focused on the dysregulation of hsa_circ_0049472 (circ_0049472) and potential functions in SK-N-SH cells with amyloid-beta peptide (Aβ) treatment in AD.

Methods: RNA expression was detected by real-time quantitative PCR. Cell viability and proliferation were measured by MTS and Edu assays. Flow cytometry was used for Apoptosis detection, and cell inflammation was assessed using enzyme-linked immunosorbent assay. Target interaction was validated by dual-luciferase reporter assay and RNA immunoprecipitation assay. Protein expression and phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) pathway were examined by Immunoblotting.

Results: Aβ treatment inhibited cell viability and proliferation of SK-N-SH cells, but enhanced Apoptosis rate, Apoptosis protein levels (Bcl2-associated X protein and cleaved-caspase-3) and inflammatory cytokines (interleukin -6, IL-1β, tumor necrosis factor-α). Then, circ_0049472 expression was shown to be upregulated in response to Aβ stimulation and knockdown of circ_0049472 has ameliorated Aβ-induced cell injury. Circ_0049472 was identified as a Sponge for miR-22-3p, and miR-22-3p inhibition reversed the regulation of circ_0049472 knockdown in Aβ-treated cells. Furthermore, ZNF217 acted as a target of miR-22-3p and circ_0049472 could regulate ZNF217 expression via binding to miR-22-3p. Overexpression of miR-22-3p abated Aβ-induced Apoptosis and inflammation via downregulating ZNF217. Furthermore, Aβ reduced proteins levels of p-PI3K and p-AKT, and this inhibition of PI3K-AKT pathway was restored by the regulation of circ_0049472/miR-22-3p/ZNF217 axis.

Conclusion: Circ_0049472 was involved in Aβ-induced neural injury by regulating miR-22-3p/ZNF217 axis to affect PI3K-AKT pathway. This study has discovered an innovative mechanism for AD.

Keywords

Aβ; Circ_0049472; MiR-22–3p; ZNF217.

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