The emerging role of microRNA-4487/6845-3p in Alzheimer’s disease pathologies is induced by Abeta25-35 triggered in SH-SY5Y cell.

Hu L, Zhang R, Yuan Q, Gao Y, Yang MQ, Zhang C, Huang J, Sun Y, Yang W, Yang JY, Min ZL, Cheng J, Deng Y, Hu X.

Citation

Hu L, Zhang R, Yuan Q, Gao Y, Yang MQ, Zhang C, Huang J, Sun Y, Yang W, Yang JY, Min ZL, Cheng J, Deng Y, Hu X. (2018) The emerging role of microRNA-4487/6845-3p in Alzheimer’s disease pathologies is induced by Abeta25-35 triggered in SH-SY5Y cell. BMC Systems Biology 12(Suppl 7):119.

Abstract

BACKGROUND:
Accumulation of amyloid beta-peptide (Abeta) is implicated in the pathogenesis and development of Alzheimer’s disease (AD). Neuron-enriched miRNA was aberrantly regulated and may be associated with the pathogenesis of AD. However, regarding whether miRNA is involved in the accumulation of Abeta in AD, the underlying molecule mechanism remains unclear. Therefore, we conduct a systematic identification of the promising role of miRNAs in Abeta deposition, and shed light on the molecular mechanism of target miRNAs underlying SH-SY5Y cells treated with Abeta-induced cytotoxicity.

RESULTS:
Statistical analyses of microarray data revealed that 155 significantly upregulated and 50 significantly downregulated miRNAs were found on the basis of log2 | Fold Change >0.585 and < 0.05 filter condition through 2588 kinds of mature miRNA probe examined. PCR results show that the expression change trend of the selected six miRNAs (miR-6845-3p, miR-4487, miR-4534, miR-3622-3p, miR-1233-3p, miR-6760-5p) was consistent with the results of the gene chip. Notably, Abeta25-35 downregulated hsa-miR-4487 and upregulated hsa-miR-6845-3p in SH-SY5Y cell lines associated with Abeta-mediated pathophysiology. Increase of hsa-miR-4487 could inhibit cells apoptosis, and diminution of hsa-miR-6845-3p could attenuate axon damage mediated by Abeta25-35 in SH-SY5Y.

CONCLUSIONS:
Together, these findings suggest that dysregulation of hsa-miR-4487 and hsa-miR-6845-3p contributed to the pathogenesis of AD associated with Abeta25-35 mediated by triggering cell apoptosis and synaptic dysfunction. It might be beneficial to understand the pathogenesis and development of clinical diagnosis and treatment of AD. Further, our well-designed validation studies will test the miRNAs signature as a prognostication tool associated with clinical outcomes in AD.