miR-27a promotion resulting from silencing of HDAC3 facilitates the recovery of spinal cord injury by inhibiting PAK6 expression in rats
Copyright © 2020 Elsevier Inc. All rights reserved..
AIMS: Spinal cord injury (SCI) is one of the most devastating diseases that challenges neurology and medicine, leading to paraplegia or quadriplegia worldwide. Neuroprotection conferred by histone deacetylase (HDAC) inhibitors against various insults and deficits in the central nervous system has been reported previously. Herein, we set out to ascertain whether HDAC3 inhibition exerts neuroprotective effects against SCI.
MAIN METHODS: A modified Allen's weight-drop method was performed to induce experimental SCI in rats. Basso-Beattie-Bresnahan (BBB) scores were used to assess locomotor function. Flow cytometric analysis of AnnexinV-FITC/PI double staining, TUNEL staining, and immunoblotting analysis of apoptosis-related proteins were performed to determine apoptosis in H2O2-induced cell injury of primary rat neurons.
KEY FINDINGS: Upregulated HDAC3 and downregulated miR-27a were observed in spinal cord tissues of SCI rats and H2O2-injured neurons. HDAC3 knockdown by its specific shRNA restored the locomotor function of SCI rats and prevented rat neurons from H2O2-induced apoptosis through promotion of miR-27a. miR-27a targeted PAK6 (encoding P21-activated kinase 6) and inhibited its expression. The effects of HDAC3 knockdown on the locomotor function of SCI rats and H2O2-induced apoptosis of rat neurons were lost upon further PAK6 overexpression.
SIGNIFICANCE: The present study uncovers that silencing HDAC3 inhibited PAK6 expression by upregulating miR-27a, eventually inhibiting neuron apoptosis and promoting the recovery of SCI, which might provide a novel therapeutic target for SCI.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:260 |
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| Enthalten in: |
Life sciences - 260(2020) vom: 01. Nov., Seite 118098 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Qingzhong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.11.2020 Date Revised 06.11.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.lfs.2020.118098 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM31255480X |
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| 100 | 1 | |a Zhou, Qingzhong |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a miR-27a promotion resulting from silencing of HDAC3 facilitates the recovery of spinal cord injury by inhibiting PAK6 expression in rats |
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| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a AIMS: Spinal cord injury (SCI) is one of the most devastating diseases that challenges neurology and medicine, leading to paraplegia or quadriplegia worldwide. Neuroprotection conferred by histone deacetylase (HDAC) inhibitors against various insults and deficits in the central nervous system has been reported previously. Herein, we set out to ascertain whether HDAC3 inhibition exerts neuroprotective effects against SCI | ||
| 520 | |a MAIN METHODS: A modified Allen's weight-drop method was performed to induce experimental SCI in rats. Basso-Beattie-Bresnahan (BBB) scores were used to assess locomotor function. Flow cytometric analysis of AnnexinV-FITC/PI double staining, TUNEL staining, and immunoblotting analysis of apoptosis-related proteins were performed to determine apoptosis in H2O2-induced cell injury of primary rat neurons | ||
| 520 | |a KEY FINDINGS: Upregulated HDAC3 and downregulated miR-27a were observed in spinal cord tissues of SCI rats and H2O2-injured neurons. HDAC3 knockdown by its specific shRNA restored the locomotor function of SCI rats and prevented rat neurons from H2O2-induced apoptosis through promotion of miR-27a. miR-27a targeted PAK6 (encoding P21-activated kinase 6) and inhibited its expression. The effects of HDAC3 knockdown on the locomotor function of SCI rats and H2O2-induced apoptosis of rat neurons were lost upon further PAK6 overexpression | ||
| 520 | |a SIGNIFICANCE: The present study uncovers that silencing HDAC3 inhibited PAK6 expression by upregulating miR-27a, eventually inhibiting neuron apoptosis and promoting the recovery of SCI, which might provide a novel therapeutic target for SCI | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Jia, Xufeng |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Daxiong |e verfasserin |4 aut | |
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