Berberine attenuates Aß42-induced neuronal damage through regulating circHDAC9/miR-142-5p axis in human neuronal cells.

BACKGROUND: Berberine plays a neuroprotective role in neurodegenerative diseases, including Alzheimer's disease (AD). Circular RNAs (circRNAs) function as crucial players in AD pathogenesis. In the current work, we aimed to investigate whether circRNA histone deacetylase 9 (circHDAC9) was involved in the regulation of berberine in AD. METHODS: Cell viability and apoptosis were determined by the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to assess caspase-3 activity and the production of interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α). The levels of circHDAC9 and miR-142-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Subcellular fractionation assays were performed to evaluate the localization of circHDAC9. The direct interaction between circHDAC9 and miR-142-5p was confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. RESULTS: Our data indicated that circHDAC9 was indeed a circular transcript and mainly localized in the cytoplasm. 42-residue ß-amyloid (Aß42) triggered a significant down-regulation in circHDAC9 and a striking up-regulation in miR-142-5p in human neuronal (HN) cells. Berberine relieved Aß42-induced HN cell neurotoxicity. Moreover, berberine resulted in increased circHDAC9 expression and decreased miR-142-5p level in Aß42-treated HN cells. Berberine alleviated Aß42-induced neuronal damage in HN cells by up-regulating circHDAC9. Furthermore, circHDAC9 acted as a molecular sponge of miR-142-5p. CircHDAC9 overexpression alleviated Aß42-induced HN cell neurotoxicity via miR-142-5p. CONCLUSION: Our current study suggested that berberine protected HN cell from Aß42-induced neuronal damage at least partly through regulating the circHDAC9/miR-142-5p axis, highlighting novel evidence for the neuroprotective effect of berberine in AD.