hsa_circ_0006916 Exerts Effect on Amyloid Beta-Induced Neuron Injury by Targeting miR-217/HOMER1

Circular RNAs (circRNAs) are rich in miRNA-binding sites, which serve as miRNA sponges or competitive endogenous RNAs (ceRNAs). In the central nervous system, circRNAs are relevant to many neurological disorders including Alzheimer's disease (AD). Dementia associated with AD is correlated with the conversion of the β-Amyloid (Aβ) peptides from soluble monomers to aggregated oligomers and insoluble fibrils. Downregulation of circHOMER1 (circ_0006916) expression level is observed in AD female cases. Thus, this study investigates whether circHOMER1 prevents fibrillar Aβ (fAβ)-induced cell damage.

The levels of sAβ₄₂ in cerebrospinal fluid (CSF) of amyloid-positive normal cognition (NC) individuals, mild cognitive impairment (MCI) individuals, and AD patients were measured. For in vitro studies, the SH-SY5Y cells were treated with 10 μM of fAβ₄₂ or soluble Aβ₄₂ (sAβ₄₂). RNase R treatment and actinomycin D treatment were used to identify the characteristics of circHOMER1. Gene expression was measured by RT-qPCR. Protein levels were measured using western blotting. Cell viability and apoptosis were estimated by MTT assays and flow cytometry. The binding relationship of miR-217 and circHOMER1 (HOMER1) was verified by luciferase reporter assays.

CircHOMER1 was more stable in SH-SY5Y cells than linear HOMER1. CircHOMER1 upregulation ameliorates the fAβ₄₂-induced cell apoptosis and circHOMER1 downregulation reversed the anti-apoptotic roles of sAβ₄₂. Mechanistically, miR-217 interacted with circHOMER1 (HOMER1). Moreover, miR-217 upregulation or HOMER1 downregulation exacerbates the fAβ₄₂-induced cell damage.

CircHOMER1 (hsa_circ_0006916) ameliorates the fAβ₄₂-induced cell injury via the miR-217/HOMER1 axis.