Silencing of lncRNA PRR34-AS1 Alleviates Alzheimer's Disease by Targeting miR-29c-3p to Regulate Microglia Inflammation.

Abstract

Objective: This study aims to investigate the role of long non-coding RNA (lncRNA) PRR34 antisense RNA 1 (PRR34-AS1) and microRNA (miR)-29c-3p in Alzheimer's disease (AD) and to explore their mechanisms.

Methods: The study included 35 AD patients and 35 healthy controls. In vitro experiments were conducted using microglial cell lines HMC3 and BV2, which were treated with Aβ25-35, and gene knockout or overexpression experiments were performed to verify the function of the target genes. PRR34-AS1 and miR-29c-3p levels in serum and cells were detected using RT-qPCR. Dual luciferase reporter assay and RNA pull-down assay were conducted to validate the interaction between PRR34-AS1 and miR-29c-3p. The CCK-8 assay and flow cytometry were used to assess cell viability and apoptosis.

Results: The findings showed that PRR34-AS1 levels were elevated in the serum of AD patients, while miR-29c-3p levels were significantly decreased, with a negative correlation observed between them. Silencing PRR34-AS1 alleviated the decline in cell viability and increase in apoptosis induced by Aβ25-35 in microglial cells and inhibited the release of pro-inflammatory factors. Additionally, a direct interaction between PRR34-AS1 and miR-29c-3p was confirmed. Silencing miR-29c-3p counteracted the anti-inflammatory effects of PRR34-AS1.

Conclusion: This study discovered that the PRR34-AS1/miR-29c-3p axis played a crucial role in the Aβ25-35-induced AD cell model. The inhibition of PRR34-AS1 can alleviate neuroinflammation and apoptosis in microglial cells, with miR-29c-3p serving as a significant mediator in this process.