miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1-containing AMPA receptors in a mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Expression of matrix metalloproteinase-9 and tension protein homologous gene(PTEN)in gingival carcinoma and its clinical significance / 中国生化药物杂志

Objective To investigate the expression and clinical significance of matrix metalloproteinase(MMP-9)and tension protein homologous gene in gingival cancer tissue.Methods 50 cases in Guyuan people's hospital from June 2013to December 2016 were selected to study the expression of matrix metalloproteinase(MMP-9)and tension protein homologous gene in gingival cancer tissue.Results The positive rate of PTEN in gingival cancer group was 54.00%, the positive rate of PTEN was 94.00% in normal tissue, normal control group positive rate of PTEN was significantly higher than that of gingival cancer group(P<0.05);the positive rate of MMP-9 in gingival cancer group was 76.00%, the positive rate of control group was 20.00%, gingival cancer group was significantly higher than the normal control group(P<0.05).The expression of MMP-9 and PTEN in in gingival cancer tissue was unrealted with gender, age, and tissue differentiation, and associated with lymph node metastasis and tissue infiltration(P<0.05).Conclusion PTEN expression is low in gingival cancer tissue low, MMP-9 expression is high in gingival cancer tissues.PTEN and MMP-9 are closely related to the incidence and development of gingival cancer.Therefore, MMP-9 positivity is a risk factor for gingival cancer, while PTEN positivity is a protective factor for gingival cancer.