Diagnostic value of miR-193a-3p in Alzheimer's disease and miR-193a-3p attenuates amyloid-β induced neurotoxicity by targeting PTEN

Exp Gerontol. 2020 Feb:130:110814. doi: 10.1016/j.exger.2019.110814. Epub 2019 Dec 16.

Abstract

Objective: Many microRNAs (miRNAs) have been reported to be aberrantly expressed in Alzheimer's disease (AD) patients. The present study aimed to explore the diagnostic value and neuroprotective role of miR-193a-3p in AD.

Methods: 108 sporadic AD patients and 93 healthy controls were included. An Aβ25-35 insult cellular AD model of PC12 and SH-SY5Y was established. The relative expression levels of miR-193a-3p were calculated using qRT-PCR. Receiver operating characteristic (ROC) curve was applied to evaluate the usefulness of miR-193a-3p for detecting AD. Cell viability and apoptotic rates were calculated. Luciferase reporter assay was performed to confirm the interaction between miR-193a-3p and PTEN.

Results: miR-193a-3p expression was downregulated in both AD patients and the cellular AD model (all P < 0.001). Remarkable positive association was detected between serum miR-193a-3p level and MMSE score in AD patients (r = 0.5889, P < 0.0001). The diagnostic sensitivity and specificity were 89.8% and 77.4%, respectively, and the area under the curve (AUC) was 0.914. Overexpression of miR-193a-3p weakened Aβ25-35 induced cell viability inhibition, and reduced Aβ25-35 induced cell apoptosis in PC12 cells (all P < 0.01). Downregulation of miR-193a-3p intensified the effect of Aβ25-35 PTEN was proved to be the target gene of miR-193a-3p.

Conclusion: MiR-193a-3p could be a novel biomarker for AD diagnosis, and may protect against neurotoxicity in AD by targeting PTEN.

Keywords: Alzheimer's disease; MiR-193a-3p; Neuroprotective; PTEN.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Apoptosis
  • Biomarkers / blood
  • Case-Control Studies
  • Down-Regulation
  • Female
  • Humans
  • Male
  • Mental Status and Dementia Tests
  • MicroRNAs / blood*
  • PC12 Cells
  • PTEN Phosphohydrolase / metabolism*
  • Peptide Fragments / metabolism*
  • Rats

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • MIRN193 microRNA, human
  • MicroRNAs
  • Peptide Fragments
  • amyloid beta-protein (25-35)
  • PTEN Phosphohydrolase
  • PTEN protein, human