RETRACTED ARTICLE: MicroRNA-322 Cluster Promotes Tau Phosphorylation via Targeting Brain-Derived Neurotrophic Factor

Abstract

Brain-derived neurotrophic factor (BDNF) is a crucial regulator to support synaptic plasticity and neuronal survival, its significant decrease is a pathophysiological hallmark in Alzheimer’s disease (AD) brains and accounts for poor prognosis. MicroRNAs (miRNAs) interfere with the translation of target mRNAs and control a variety of physiological and pathological processes. MiR-322 is the rodent homologue of human miR-424, it is involved in the modulation of cell differentiation, proliferation, apoptosis and metabolic activities in diverse tissues and organs. However, the roles and potential mechanisms of miR-322 remain elusive in AD pathogenesis. Here we observed miR-322 is significantly increased along with BDNF decrease in AD mouse brain. Bioinformatics prediction implicated that BDNF 3′-untranslated region (3′-UTR) possesses the putative target sequence of miR-322. Luciferase reporter assay identified that miR-322 can directly conjugate to BDNF 3′-UTR. The functional research showed that MiR-322 input deregulates BDNF expression at either mRNA or protein levels, whereas miR-322 silence restores BDNF expression in vitro. Furthermore, we found miR-322 promotes Tau phosphorylation via negatively controlling BDNF–TrkB receptor activation, otherwise MiR-322 silence restores TrkB activation and attenuates tau phosphorylation. Collectively, this study demonstrated a novel miRNA-dependent manner of BDNF degradation in AD pathogenesis, it may drive a miRNAs- or BDNF based therapeutic strategies against Alzheimer’s disease.

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Change history

  • 25 June 2020

    The Editors have retracted this article [1] following an investigation conducted by the journal. After publication concerns were raised regarding interpretation of the data presented in Fig. 4. The Editors requested additional data and clarification to confirm interpretation of data results. After further review, the Editors found that the additional data were not adequate to support the conclusion of the article and that P-values for the additional data were based on improper statistical analyses. With more appropriate statistical analysis, the reported effects for miR-322 and BDNF were not statistically significant. Dr. Chichu Xie agrees to this retraction. None of the other authors have responded to any correspondence from the publisher about this retraction.

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Acknowledgements

This project was granted by the Science and Technology Foundation of Guizhou Province (TN2015-60; J-2014-2017) and the National Health and Family Planning Commission of Guizhou Province (WT2017-14).

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Correspondence to Shiqi Long.

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The authors have no relevant financial conflicts of interest to declare.

Additional information

The Editors have retracted this article following an investigation conducted by the journal. After publication concerns were raised regarding interpretation of the data presented in Fig 4. The Editors requested additional data and clarification to confirm interpretation of data results. After further review, the Editors found that the additional data were not adequate to support the conclusion of the article and that P-values for the additional data were based on improper statistical analyses. With more appropriate statistical analysis, the reported effects for miR-322 and BDNF were not statistically significant. Dr. Chichu Xie agrees to this retraction. None of the other authors have responded to any correspondence from the publisher about this retraction.

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Zhang, J., Liu, Z., Pei, Y. et al. RETRACTED ARTICLE: MicroRNA-322 Cluster Promotes Tau Phosphorylation via Targeting Brain-Derived Neurotrophic Factor. Neurochem Res 43, 736–744 (2018). https://doi.org/10.1007/s11064-018-2475-1

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Keywords

  • MicroRNA-322
  • BDNF–TrkB signal
  • Tau phosphorylation
  • Alzheimer’s disease