Journal
INTERNATIONAL JOURNAL OF NEUROSCIENCE
Volume 131, Issue 5, Pages 425-432Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/00207454.2020.1746307
Keywords
Alzheimer's disease; lncRNA RPPH1; miR-326; endoplasmic reticulum stress; apoptosis; pyruvate kinase M2
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Funding
- Youth Science Foundation [81401083]
- Joint Fund Project of Guizhou Province [Qian Ke He LH [2014]7022]
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The study demonstrated that lncRNA RPPH1 can attenuate A beta(25-35)-induced ERS and apoptosis in SH-SY5Y cells by regulating the miR-326/PKM2 axis, improving cell viability. This provides therapeutic options for AD patients.
Background: The durative endoplasmic reticulum stress (ERS) and subsequent apoptosis contributes to the development and progression of Alzheimer's disease (AD). MiR-326 can reduce pyruvate kinase M2 (PKM2) expression, leading to ERS. Whereas, lncRNA RPPH1 is able to increase dendritic spine density and protect hippocampal pyramidal neurons through targeting miR-326. Our study aims to investigate the regulation of lncRNA RPPH1 and miR-326/PKM2 on ERS and related apoptosis in AD. Methods: SH-SY5Y cells treated with A beta(25-35) were selected as an in vitro AD model. RPPH1 and miR-326 overexpression and silencing cells were established by transforming vectors. The expression of RPPH1 and miR-326 were detected by qRT-PCR. MTT, flow cytometric, intracellular calcium assay and Western blot were used to test the functions of RPPH1 and miR-326 in SH-SY5Y cell proliferation, apoptosis and ERS. Dual-luciferase assay was used to detect the interaction among RPPH1, miR-326 and PKM2. Results: RPPH1 overexpression enhanced the viability of SH-SY5Y cells, and attenuated the apoptosis of of SH-SY5Y cells. Moreover, RPPH1 overexpression down-regulated ER stress related proteins such as GRP78, CHOP and cleaved caspase-12. Mechanistically, RPPH1 directly targeted miR-326, thereby counteracting its inhibitory effect on PKM2 expression, contributing to attenuation of apoptosis and ERS induced by A beta(25-35). Conclusion: A beta(25-35)-induced ERS and apoptosis in SH-SY5Y cells can be attenuated by lncRNA RPPH1 through regulating miR-326/PKM2 axis. This study provided therapeutic options for AD patients.
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