부산대학교 도서관

Alzheimer's disease (AD) is a neurodegenerative disease that seriously affects the life and health of the elderly. Studies have found that circular RNAs (circRNAs) are associated with human diseases, including AD. Hsa_circ_0049472 has been uncovered to be overexpressed in AD, but the role of circ_0049472 remains unclear. AD patients were recruited to collect cerebrospinal fluid (CSF) and serum samples. Amyloid beta (A[beta])-induced SK-N-SH and CHP-212 cells were used as the AD cell models in vitro. Quantitative real-time PCR (qRT-PCR) was used to assess the expression of circ_0049472, microRNA-107 (miR-107) and kinesin family member 1B (KIF1B). Cell counting kit-8 assay tested the cell viability, and flow cytometry measured cell apoptosis. The levels of proliferating cell nuclear antigen (PCNA), BCL2 Associated X (Bax) and kinesin family member 1B (KIF1B) protein were examined by western blot. In addition, the relative inflammatory cytokines (TNF-[alpha], IL-6 and IL-1[beta]) were detected by enzyme-linked immunosorbent assay (ELISA). The malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured by relative kits. Dual-luciferase reporter assays and RNA pull-down assay verified the relationship between miR-107 and circ_0049472 or KIF1B. Circ_0049472 and KIF1B were overexpressed in AD patient-derived cerebrospinal fluid (CSF) and serum samples, as well as A[beta]-induced SK-N-SH and CHP-212 cells. Silencing circ_0049472 promoted cell proliferation, and inhibited cell apoptosis in A[beta]-induced SK-N-SH and CHP-212 cells. MiR-107 was a target of circ_0049472. MiR-107 silencing abolished the cell viability and apoptosis affected by down-regulation of circ_0049472 in A[beta]-induced SK-N-SH and CHP-212 cells. Besides, miR-107 targeted KIF1B, and overexpressed KIF1B reverted miR-107 elevation-mediated effects on cell apoptosis, inflammation, and oxidative stress of A[beta]-induced SK-N-SH and CHP-212 cells. Circ_0049472 modulated KIF1B by serving as a miR-107 decoy, thereby mediating A[beta]-induced neurotoxicity, suggesting that circ_0049472 may be involved in AD pathogenesis.
Author(s): Chaosheng Zeng [sup.1] , Huaijie Xing [sup.1] , Min Chen [sup.1] , Lin Chen [sup.1] , Pengxiang Li [sup.1] , Xiaowen Wu [sup.1] , Li Li [sup.1] Author Affiliations: [...]