ABSTRACT
This study explored the influence of long non-coding RNA (lncRNA) SNHG14 on α-synuclein (α-syn) expression and Parkinson's disease (PD) pathogenesis. Firstly, we found that the expression level of SNHG14 was elevated in brain tissues of PD mice. In MN9D cells, the rotenone treatment (1µmol/L) enhanced the binding between transcriptional factor SP-1 and SNHG14 promoter, thus promoting SNHG14 expression. Interference of SNHG14 ameliorated the DA neuron injury induced by rotenone. Next, we found an interaction between SNHG14 and miR-133b. Further study showed that miR-133b down-regulated α-syn expression by targeting its 3'-UTR of mRNA and SNHG14 could reverse the negative effect of miR-133b on α-syn expression. Interference of SNHG14 reduced rotenone-induced DA neuron damage through miR-133b in MN9D cells and α-syn was responsible for the protective effect of miR-133b. Similarly, interference of SNHG14 mitigated neuron injury in PD mouse model. All in all, silence of SNHG14 mitigates dopaminergic neuron injury by down-regulating α-syn via targeting miR-133b, which contributes to improving PD.
Subject(s)
Dopaminergic Neurons , Intracellular Signaling Peptides and Proteins/metabolism , MicroRNAs/metabolism , Nerve Tissue Proteins/metabolism , Parkinson Disease, Secondary/etiology , alpha-Synuclein/metabolism , Animals , Cell Line , Disease Models, Animal , Mice, Inbred C57BL , Parkinson Disease, Secondary/metabolism , RNA, Long Noncoding/metabolism , RotenoneABSTRACT
Epilepsy is a common neurological disorder in the central nervous system. Inflammation disrupts the blood-brain barrier (BBB), which is responsible for maintaining brain homeostasis. This study was aimed to investigate the functional role of microRNA (miR)-132 in hippocampal HT-22 cells under lipopolysaccharide (LPS) stimulation. In vitro cell inflammatory model was constructed by LPS stimulation. Inflammatory cell injury was evaluated according to the alterations of cell viability, apoptosis, and expression of inflammatory cytokines. Then, miR-132 level after LPS treatment was assessed. Subsequently, miR-132 was abnormally expressed after cell transfection, and the effects of miR-132 on LPS-induced cell inflammatory injury as well as phosphorylated levels of key kinases in the NF-κB and MAPK kinase (MEK)/ERK pathways were determined. The target gene of miR-132 was virtually screened and verified, and whether miR-132 affected HT-22 cells under LPS stimulation through regulating the target gene was verified. The results showed that the level of miR-132 was down-regulated by LPS in HT-22 cells, and the LPS-induced inflammatory injury could be reduced by miR-132 overexpression. Then, the phosphorylated levels of kinases in the NF-κB and MEK/ERK pathways were decreased by miR-132 overexpression. Tumor necrosis factor receptor-associated factor 6 (TRAF6) was predicted and verified to be a target of miR-132. Moreover, the alterations induced by miR-132 overexpression in the LPS-treated HT-22 cells were abrogated by TRAF6 overexpression. Therefore, we drew the conclusion that LPS down-regulated miR-132 and miR-132 attenuated LPS-induced inflammatory cell injury by targeting TRAF6, along with the inhibition of the NF-κB and MEK/ERK pathways.
