Research Papers:

MiR-144 promotes β-amyloid accumulation-induced cognitive impairments by targeting ADAM10 following traumatic brain injury

Liqian Sun _, Manman Zhao, Jingbo Zhang, Aihua Liu, Wenjun Ji, Youxiang Li, Xinjian Yang and Zhongxue Wu

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Oncotarget. 2017; 8:59181-59203. https://doi.org/10.18632/oncotarget.19469

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Liqian Sun1,*, Manman Zhao2,*, Jingbo Zhang1, Aihua Liu1, Wenjun Ji1, Youxiang Li1, Xinjian Yang1 and Zhongxue Wu1

1Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R.China

2Department of Histology and Embryology, School of Basic Medical Science, North China University of Science and Technology, Tangshan 063000, P.R.China

*These authors have contributed equally to this work

Correspondence to:

Liqian Sun, email: [email protected]

Keywords: miR-144, ADAM10, TBI, cognitive impairment, β-amyloid

Received: December 12, 2016    Accepted: June 19, 2017    Published: July 22, 2017


The dysregulation expression of microRNAs (miRNAs) including miR-144, has been widely documented in TBI. However, little is known about the potential roles of miR-144 in the pathogenesis of TBI. In this study, we investigated the potential effects of miR-144 on cognitive function in vivo and in vitro. The results indicated that inhibition of miR-144 conferred a better neurological outcome after TBI in vivo, as evidenced by reduced lesion volume, alleviated brain edema and increased mNSS, of particular importance, improved cognitive deficits. In vitro, miR-144 knockdown protected neuron against Glu-induced injury, by enhancing cell viability, suppressing LDH release and caspase-3 activity, and reducing cognitive-related proteins levels. However, overexpression of miR-144 in vivo and in vitro showed the opposite effects. To further explore the molecular mechanisms underlying miR-144-induced cognitive dysfunctions, we found a significant inverse correlation between miR-144 and ADAM10 expression. Moreover, the direct interaction between miR-144 and ADAM10 3’-UTR was identified by dual-luciferase reporter assay. Also, we found miR-144 negatively regulated ADAM10 protein expression. Additionally, ADAM10 could modulate β-amyloid formation involved in cognitive deficits. Notably, ADAM10 knockdown by siRNA apparently abrogated miR-144 inhibitor-mediated neuroprotection. Taken together, these findings demonstrated that elevated miR-144 promoted cognitive impairments induced by β-amyloid accumulation post-TBI through suppressing of ADAM10 expression.

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