Tau hyperphosphorylation is involved in the progression of Alzheimer’s disease (AD). In this study, we aimed to evaluate the role of linc00507 in modulating Tau phosphorylation in AD animal and Aβ42-SH-SY5Y cell model.
APP/PS transgenic mice and Aβ42-SH-SY5Y cell model were used to study the role of linc00507 in AD. qRT-PCR evaluated the RNA expression of linc00507, miR-181c-5p and MAPT/TTBK1. The interactions between the genes were studied through changes in one gene expression by regulating another gene in cells and meanwhile correlation assays were performed in mice. Western blot assays examined the protein expression of MAPT/TTBK1, phosphorylation of tau and signaling proteins P25/P35/GSK3β in response to the regulation of linc00507, miR-181c-5p and MAPT/TTBK1 in cells and also mice.
Linc00507 was significantly elevated in hippocampus, and cerebral cortex of APP/PS transgenic mice and AD-like SH-SY5Y cells. it could bind miR-181c-5p and thereby regulate the expression of microtubule-associated protein Tau (MAPT) and tau-tubulin kinase-1 (TTBK1) as a competitive endogenous RNA (ceRNA). MAPT (encoding the tau protein) and TTBK1 (encoding a tau kinase) were identified as direct target genes of miR-181c-5p. Furthermore, Linc00507 mediated tau protein hyperphosphorylation by the activation of the P25/P35/GSK3β signaling pathway through regulating MAPT/TTBK1 by sponging miR-181c-5p.
Our findings highlight the regulatory role of linc00507 in tau phosphorylation miR-181c-5p as ceRNA of MAPT/TTBK1 in vitro and in vivo, providing a basis for novel diagnostic and treatment strategies for AD.
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