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Micro-RNA-137 Inhibits Tau Hyperphosphorylation in Alzheimer’s Disease and Targets the CACNA1C Gene in Transgenic Mice and Human Neuroblastoma SH-SY5Y Cells

Yang Jiang, Bing Xu, Jing Chen, Yi Sui, Li Ren, Jing Li, Huiyu Zhang, Liqing Guo, Xiaohong Sun

(Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland))

Med Sci Monit 2018; 24:5635-5644

DOI: 10.12659/MSM.908765

Published: 2018-08-13

BACKGROUND: Alzheimer’s disease (AD) results in cognitive impairment. The calcium voltage-gated channel subunit alpha-1 C CACNA1C gene encodes an alpha-1 C subunit of L-type calcium channel (LTCC). The aim of this study was to investigate the role of micro-RNA-137 (miR-137) and the CACNA1C gene in APPswe/PS1ΔE9 (APP/PS1) double-transgenic AD mice and in human neuroblastoma SH-SY5Y cells.
MATERIAL AND METHODS: Six-month-old APP/PS1 double-transgenic AD mice (N=6) and age-matched normal C57BL/6 mice (N=6) underwent a Morris water maze (MWM) test, expression levels of amyloid-β (Aβ), LTCC, the CACNA1C gene, and miR-137 were measured in the rat hippocampus and cerebral cortex in both groups of mice. A luciferase assay was used to evaluate the effect of miR-137 on the expression of CACNA1C in SH-SY5Y human neuroblastoma SH-SY5Y cells. Western blotting was used to detect the CACNA1C, phosphorylated-tau (p-tau), and Aβ proteins.
RESULTS: In APP/PS1 transgenic AD mice, spatial learning and memory was significantly reduced, levels of Aβ1–40 and Aβ1–42 were increased in the serum, hippocampus, and cerebral cortex, expression levels of miR-137 were reduced, expression of CACNA1C protein was increased in the hippocampus and cerebral cortex, compared with normal control mice. miR-137 regulated the expression of the CACNA1C gene. Increased expression levels of p-tau (Ser202, Ser396, and Ser404) induced by Aβ1–42 were inhibited by miR-137 mimics in SH-SY5Y human neuroblastoma cells in vitro.
CONCLUSIONS: In a transgenic mouse model of AD, miR-137 and expression of the CACNA1C gene inhibited the hyperphosphorylation of tau protein.

Keywords: 14-3-3 Proteins, Alzheimer Disease, Amyloid beta-Peptides