Circular RNA cerebellar degeneration-related protein 1 antisense RNA (Circ-CDR1as) downregulation induced by dexmedetomidine treatment protects hippocampal neurons against hypoxia/reoxygenation injury through the microRNA-28-3p (miR-28-3p)/tumor necrosis factor receptor-associated factor-3 (TRAF3) axis

Cerebral ischemia/reperfusion (CI/R) injury results in serious brain tissue damage, thereby leading to long-term disability and mortality. It has been reported that dexmedetomidine (DEX) exerted neuroprotective effects in CI/R injury. Herein, we intended to investigate whether and how circular RNA (...

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Autores principales:	Junhua Wang, Ying Wang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	dexmedetomidine circrna cdr1as mir-28-3p traf3 hippocampal neuronal dysfunction Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/cc0b043e617c49ed96dd799545fe908a
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spelling	oai:doaj.org-article:cc0b043e617c49ed96dd799545fe908a2021-11-26T11:19:49ZCircular RNA cerebellar degeneration-related protein 1 antisense RNA (Circ-CDR1as) downregulation induced by dexmedetomidine treatment protects hippocampal neurons against hypoxia/reoxygenation injury through the microRNA-28-3p (miR-28-3p)/tumor necrosis factor receptor-associated factor-3 (TRAF3) axis2165-59792165-598710.1080/21655979.2021.1999369https://doaj.org/article/cc0b043e617c49ed96dd799545fe908a2021-11-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1999369https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Cerebral ischemia/reperfusion (CI/R) injury results in serious brain tissue damage, thereby leading to long-term disability and mortality. It has been reported that dexmedetomidine (DEX) exerted neuroprotective effects in CI/R injury. Herein, we intended to investigate whether and how circular RNA (circRNA) cerebellar degeneration-related protein 1 antisense RNA (circ-CDR1as) was involved in the DEX-mediated protection on hippocampal neurons. In our work, the mouse hippocampal neuronal cells (HT-22) were used to construct a hypoxia/reperfusion (H/R) model for CI/R injury. Cell proliferation and apoptosis were evaluated by CCK-8 and flow cytometry. Gene expressions were detected by RT-qPCR. Levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) were measured by ELISA. The association between miR-28-3p and circ-CDR1as or TRAF3 was verified by dual-luciferase assay. The results indicated that DEX alleviated HT-22 cell dysfunction induced by H/R treatment. In addition, circ-CDR1as was downregulated after DEX treatment and reversed the effects of DEX on the proliferation, apoptosis, and inflammatory responses of H/R-treated HT-22 cells. Circ-CDR1as positively regulated TRAF3 expression via interaction with miR-28-3p in HT-22 cells. Circ-CDR1as aggravated H/R-treated HT-22 cell dysfunction through targeting miR-28-3p. Furthermore, TRAF3 inhibition partly abolished the effect of circ-CDR1as overexpression on cellular activities of H/R-treated HT-22 cells. To sum up, our findings, for the first time, demonstrated that DEX exerted neuroprotective effects on hippocampal neurons against H/R treatment via the circ-CDR1as/miR-28-3p/TRAF3 regulatory network, providing novel therapeutic targets for DEX administration in CI/R treatment.Junhua WangYing WangTaylor & Francis Grouparticledexmedetomidinecircrna cdr1asmir-28-3ptraf3hippocampal neuronal dysfunctionBiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dexmedetomidine circrna cdr1as mir-28-3p traf3 hippocampal neuronal dysfunction Biotechnology TP248.13-248.65
spellingShingle	dexmedetomidine circrna cdr1as mir-28-3p traf3 hippocampal neuronal dysfunction Biotechnology TP248.13-248.65 Junhua Wang Ying Wang Circular RNA cerebellar degeneration-related protein 1 antisense RNA (Circ-CDR1as) downregulation induced by dexmedetomidine treatment protects hippocampal neurons against hypoxia/reoxygenation injury through the microRNA-28-3p (miR-28-3p)/tumor necrosis factor receptor-associated factor-3 (TRAF3) axis
description	Cerebral ischemia/reperfusion (CI/R) injury results in serious brain tissue damage, thereby leading to long-term disability and mortality. It has been reported that dexmedetomidine (DEX) exerted neuroprotective effects in CI/R injury. Herein, we intended to investigate whether and how circular RNA (circRNA) cerebellar degeneration-related protein 1 antisense RNA (circ-CDR1as) was involved in the DEX-mediated protection on hippocampal neurons. In our work, the mouse hippocampal neuronal cells (HT-22) were used to construct a hypoxia/reperfusion (H/R) model for CI/R injury. Cell proliferation and apoptosis were evaluated by CCK-8 and flow cytometry. Gene expressions were detected by RT-qPCR. Levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) were measured by ELISA. The association between miR-28-3p and circ-CDR1as or TRAF3 was verified by dual-luciferase assay. The results indicated that DEX alleviated HT-22 cell dysfunction induced by H/R treatment. In addition, circ-CDR1as was downregulated after DEX treatment and reversed the effects of DEX on the proliferation, apoptosis, and inflammatory responses of H/R-treated HT-22 cells. Circ-CDR1as positively regulated TRAF3 expression via interaction with miR-28-3p in HT-22 cells. Circ-CDR1as aggravated H/R-treated HT-22 cell dysfunction through targeting miR-28-3p. Furthermore, TRAF3 inhibition partly abolished the effect of circ-CDR1as overexpression on cellular activities of H/R-treated HT-22 cells. To sum up, our findings, for the first time, demonstrated that DEX exerted neuroprotective effects on hippocampal neurons against H/R treatment via the circ-CDR1as/miR-28-3p/TRAF3 regulatory network, providing novel therapeutic targets for DEX administration in CI/R treatment.
format	article
author	Junhua Wang Ying Wang
author_facet	Junhua Wang Ying Wang
author_sort	Junhua Wang
title	Circular RNA cerebellar degeneration-related protein 1 antisense RNA (Circ-CDR1as) downregulation induced by dexmedetomidine treatment protects hippocampal neurons against hypoxia/reoxygenation injury through the microRNA-28-3p (miR-28-3p)/tumor necrosis factor receptor-associated factor-3 (TRAF3) axis
title_short	Circular RNA cerebellar degeneration-related protein 1 antisense RNA (Circ-CDR1as) downregulation induced by dexmedetomidine treatment protects hippocampal neurons against hypoxia/reoxygenation injury through the microRNA-28-3p (miR-28-3p)/tumor necrosis factor receptor-associated factor-3 (TRAF3) axis
title_full	Circular RNA cerebellar degeneration-related protein 1 antisense RNA (Circ-CDR1as) downregulation induced by dexmedetomidine treatment protects hippocampal neurons against hypoxia/reoxygenation injury through the microRNA-28-3p (miR-28-3p)/tumor necrosis factor receptor-associated factor-3 (TRAF3) axis
title_fullStr	Circular RNA cerebellar degeneration-related protein 1 antisense RNA (Circ-CDR1as) downregulation induced by dexmedetomidine treatment protects hippocampal neurons against hypoxia/reoxygenation injury through the microRNA-28-3p (miR-28-3p)/tumor necrosis factor receptor-associated factor-3 (TRAF3) axis
title_full_unstemmed	Circular RNA cerebellar degeneration-related protein 1 antisense RNA (Circ-CDR1as) downregulation induced by dexmedetomidine treatment protects hippocampal neurons against hypoxia/reoxygenation injury through the microRNA-28-3p (miR-28-3p)/tumor necrosis factor receptor-associated factor-3 (TRAF3) axis
title_sort	circular rna cerebellar degeneration-related protein 1 antisense rna (circ-cdr1as) downregulation induced by dexmedetomidine treatment protects hippocampal neurons against hypoxia/reoxygenation injury through the microrna-28-3p (mir-28-3p)/tumor necrosis factor receptor-associated factor-3 (traf3) axis
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/cc0b043e617c49ed96dd799545fe908a
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