MicroRNA-425-5p promotes tau phosphorylation and cell apoptosis in Alzheimer’s disease by targeting heat shock protein B8

Yuan, Jiao; Wu, Yanpeng; Li, Lü; Liu, Chuanqin

doi:10.1007/s00702-019-02134-5

Cited by 27 publications

(26 citation statements)

References 26 publications

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“…Thus, RA must post-transcriptionally act on HSPB8 mRNA through a RA-induced factor in MCF-7 cells (and not in MDA-MB-231 cells), such as a miRNA, capable of decreasing HSPB8 mRNA levels and preventing its translation into the protein. Some miRNAs are capable of binding to HSPB8 mRNA (33,34), but those of our interest should be also regulated by RA. MiRNAs targeting the 3'-UTR or 5'-UTR were excluded since both regions are absent in our HSPB8 plasmid; therefore the putative miRNA must directly target the ORF region of HSPB8 mRNA.…”

Section: Discussionmentioning

confidence: 99%

Retinoic Acid Downregulates HSPB8 Gene Expression in Human Breast Cancer Cells MCF-7

et al. 2021

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Breast cancer (BC) is a serious and widespread disease for which different treatments have been developed. In addition to the classic therapies, the treatment with retinoic acid (RA) is still being clinically investigated. RA reduces cancer cells proliferation and migration, but its molecular mechanism of action is not clear. In tumor development, autophagy promotes cancer cell survival and prevents apoptosis. Small heat shock protein B8 (HSPB8) acts together with its co-chaperone BCL-2 associated athanogene 3 (BAG3) stimulating BC proliferation and migration. We analyzed whether direct correlations exist between RA and HSPB8 or BAG3 and how this may play a role in BC. We measured HSPB8 and BAG3 gene expression in MCF-7 BC cells and we analyzed the potential correlation between the antiproliferative and antimigratory effect of RA with the expression level of HSPB8. We found that in MCF-7 cells RA reduces both HSPB8 and BAG3 gene expression and it alters the mitotic spindle organization. Notably, the effects of RA on HSPB8 levels are exerted at both transcriptional and translational levels. RA effects are possibly mediated by miR-574-5p that targets the HSPB8 transcript. Our results suggest that therapeutic doses of RA can efficiently counteract the adverse effects of HSPB8 in BC progression.

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Section: Discussionmentioning

confidence: 99%

Retinoic Acid Downregulates HSPB8 Gene Expression in Human Breast Cancer Cells MCF-7

et al. 2021

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“…Similarly, overexpression of microRNA-125b results in tau hyperphosphorylation by targeting phosphatases DUSP6 and PPP1CA (124). In HEK293/tau cells, microRNA-425-5p overexpression promotes tau phosphorylation through targeting HSPB8 in AD (125). MicroRNA-132, the most significantly downregulated microRNA in AD, is associated with lower levels of tau phosphorylation by regulating EP300, GSK3b, Rbfox1, proteases Calpain2, and caspases 3/7 (126).…”

Section: Non-coding Rnas In Admentioning

confidence: 99%

Epigenetics: Recent Advances and Its Role in the Treatment of Alzheimer's Disease

2020

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“…miR-425-5p is another upregulated miRNA in patients with AD and the cellular model of AD. Upregulation of miR-425-5p has induced cell apoptosis, stimulated expression of GSK-3β, and enhanced tau phosphorylation through targeting HSPB8 (Yuan et al, 2020). miR-146a is also upregulated in AD and participates in the pathogenesis of this condition via targeting Lrp2 and inhibiting the Akt signaling pathway, modulating ROCK1 expression and decreasing Tau phosphorylation, and influencing inflammatory responses via modulation of IRAK-1 (Cui et al, 2010;Wang et al, 2016).…”

Section: Dysregulated Mirnas In Admentioning

confidence: 99%

“…miR-138 and miR-425-5p are increased in Alzheimer's disease. These miRNAs regulate the expression of GSK-3β and enhance Tau phosphorylation (Wang et al, 2015b;Yuan et al, 2020). In addition, downregulation of miR-132 and upregulation of miR-125b and miR-922 leads to Tau hyperphosphorylation (Zhao et al, 2014;Salta et al, 2016;Ma et al, 2017).…”

Section: Prognostic and Diagnostic Role Of Mirnas In Admentioning

confidence: 99%

The Eminent Role of microRNAs in the Pathogenesis of Alzheimer's Disease

Samadian

Gholipour

Hajiesmaeili

et al. 2021

Front. Aging Neurosci.

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Alzheimer's disease (AD) is an irrevocable neurodegenerative condition characterized by the presence of senile plaques comprising amassed β-amyloid peptides (Aβ) and neurofibrillary tangles mainly comprising extremely phosphorylated Tau proteins. Recent studies have emphasized the role of microRNAs (miRNAs) in the development of AD. A number of miRNAs, namely, miR-200a-3p, miR-195, miR-338-5p, miR-34a-5p, miR-125b-5p, miR-132, miR-384, miR-339-5p, miR-135b, miR-425-5p, and miR-339-5p, have been shown to participate in the development of AD through interacting with BACE1. Other miRNAs might affect the inflammatory responses in the course of AD. Aberrant expression of several miRNAs in the plasma samples of AD subjects has been shown to have the aptitude for differentiation of AD subjects from healthy subjects. Finally, a number of AD-modifying agents affect miRNA profile in cell cultures or animal models. We have performed a comprehensive search and summarized the obtained data about the function of miRNAs in AD in the current review article.

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MicroRNA-425-5p promotes tau phosphorylation and cell apoptosis in Alzheimer’s disease by targeting heat shock protein B8

Cited by 27 publications

References 26 publications

Retinoic Acid Downregulates HSPB8 Gene Expression in Human Breast Cancer Cells MCF-7

Retinoic Acid Downregulates HSPB8 Gene Expression in Human Breast Cancer Cells MCF-7

Epigenetics: Recent Advances and Its Role in the Treatment of Alzheimer's Disease

The Eminent Role of microRNAs in the Pathogenesis of Alzheimer's Disease

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