Identification of miRNAs Involved in the Protective Effect of Sevoflurane Preconditioning Against Hypoxic Injury in PC12 Cells

Sun, Yingying; Li, Yuanhai; Liu, Lei; Wang, Yiqiao; Xia, Yingjing; Zhang, Lingli; Ji, Xuewu

doi:10.1007/s10571-015-0205-7

Cited by 17 publications

(17 citation statements)

References 30 publications

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“…Overexpression of miR-101a increased apoptosis. In contrast, overexpression of miR-34b increased cell viability and this was further confirmed when inhibition of miR-34b increased the number of the apoptotic cells (Sun et al, 2015b). Interestingly, a recent study from our lab showed that resveratrol PC does not alter miRNAs in mouse brain (Lopez et al, 2016).…”

Section: Micrornas and Ischemic Preconditioningmentioning

confidence: 86%

Non-coding RNAs and neuroprotection after acute CNS injuries

Chandran

Mehta

2017

Neurochemistry International

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Accumulating evidence indicates that various classes of non-coding RNAs (ncRNAs) including microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs) and long non-coding RNAs (lncRNAs) play important roles in normal state as well as the diseases of the CNS. Interestingly, ncRNAs have been shown to interact with messenger RNA, DNA and proteins, and these interactions could induce epigenetic modifications and control transcription and translation, thereby adding a new layer of genomic regulation. The ncRNA expression profiles are known to be altered after acute CNS injuries including stroke, traumatic brain injury and spinal cord injury that are major contributors of morbidity and mortality worldwide. Hence, a better understanding of the functional significance of ncRNAs following CNS injuries could help in developing potential therapeutic strategies to minimize the neuronal damage in those conditions. The potential of ncRNAs in blood and CSF as biomarkers for diagnosis and/or prognosis of acute CNS injuries has also gained importance in the recent years. This review highlighted the current progress in the understanding of the role of ncRNAs in initiation and progression of secondary neuronal damage and their application as biomarkers after acute CNS injuries.

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Section: Micrornas and Ischemic Preconditioningmentioning

confidence: 86%

Non-coding RNAs and neuroprotection after acute CNS injuries

Chandran

Mehta

2017

Neurochemistry International

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“…Patients with low level of miR‐101a were at high risk of impaired contractility of left ventricle, indicating miR‐101 as a potential biomarker for acute myocardial infarction . Besides, a study has demonstrated that sevoflurane preconditioning‐induced neuroprotection was attenuated by miR‐101a overexpression, implying miR‐101a as a key miRNA in aggravating nerve damage during hypoxia . In the current study, miR‐101a was confirmed as a target of lncRNA EFNA3 by performing qRT‐PCR, RNA pull‐down, and RNA immunoprecipitation.…”

Section: Discussionmentioning

confidence: 99%

Retracted: Deletion of long noncoding RNA EFNA3 aggravates hypoxia‐induced injury in PC‐12 cells by upregulation of miR‐101a

Gong

Qie

Huang

et al. 2018

J of Cellular Biochemistry

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Long noncoding RNAs (lncRNAs) have been reported to be involved in several neurological pathogenesis conditions including cerebral ischemia. In the current study, the functions of lncRNA EFNA3 on hypoxia-injured rat adrenal pheochromocytoma (PC-12) cells and the underlying molecular mechanism were studied. The expression of lncRNA EFNA3 was silenced by short hairpin RNA transfection, after which the cells were subjected with hypoxia. Cell viability, migration, invasion, and apoptosis were, respectively, determined by trypan blue staining, Transwell assay, annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double-staining, and Western blot analysis. The cross regulation between lncRNA EFNA3 and miR-101a, as well as between miR-101a and Rho associated coiled-coil containing protein kinase 2 (ROCK2) were detected by performing quantitative real-time polymerase chain reaction, RNA pull-down, RNA immunoprecipitation, luciferase activity assay, and Western blot analysis. Studies showed that lncRNA EFNA3 was highly expressed in response to hypoxia. Deletion of lncRNA EFNA3 significantly aggravated hypoxia-induced injury in PC-12 cells, as the impairment of cell viability, migration, and invasion, and the inducement of apoptosis. LncRNA EFNA3 worked as a sponging molecule for miR-101a and miR-101a suppression-protected PC-12 cells against hypoxia-induced injury even when lncRNA EFNA3 was silenced. ROCK2 was a target gene of miR-101a. ROCK2 overexpression exhibited neuroprotective activities. Besides, ROCK2 overexpression activated Wnt/β-catenin pathway whereas it deactivated JAK/STAT pathway upon hypoxia. Our study suggests that deletion of lncRNA EFNA3 aggravates hypoxia-induced injury in PC-12 cells by upregulating miR-101a, which further targets ROCK2.

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“…To date, the molecular mechanisms underlying sevoflurane-induced neurotoxicity have not been fully elucidated. However, a number of studies have demonstrated that exposure to sevoflurane induces alterations in the microRNA (miR) expression profile (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane‑induced neurotoxicity is driven by OXR1 post‑transcriptional downregulation involving hsa‑miR‑302e

et al. 2018

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Sevoflurane is a common anesthetic agent used in surgical settings and previous studies have indicated that it exerts a neurotoxic effect. However, the molecular mechanism underlying this side effect is unknown. In addition, the human microRNA‑302 (hsa‑miR‑302) family members have been reported to be involved in neuronal cell development and biology. Thus, the present study aimed to investigate the potential implication of hsa‑miR‑302e in the sevoflurane‑induced cytotoxicity on human hippocampal cells (HN‑h). HN‑h cells were transfected with hsa‑miR‑302e mimic, hsa‑miR‑302e inhibitor or negative controls and subsequently exposed to different concentrations of sevoflurane. An MTT assay was used to assess the cytotoxicity of sevoflurane on HN‑h cells. Cell apoptosis was determined by flow cytometry. The levels of lactate dehydrogenase release, reactive oxygen species, lipid peroxidation and intracellular calcium (Ca2+) were additionally detected. Reverse transcription‑quantitative polymerase chain reaction and western blotting were conducted to determine mRNA and protein expression, respectively. A luciferase assay was performed for validating the targeting of OXR1 by hsa‑miR‑302e. The results indicated that sevoflurane induced a decrease in cell viability, malondialdehyde and reactive oxygen species production, lactate dehydrogenase release, intracellular Ca2+ production, calcium/calmodulin‑dependent protein kinase II phosphorylation and apoptosis. In addition, treatment with sevoflurane induced the expression of hsa‑miR‑302e while the expression of its target, oxidation resistance gene 1 (OXR1), was significantly downregulated. Inhibition of hsa‑miR‑302e expression protected neuronal cells from sevoflurane cytotoxicity. Mechanistic studies demonstrated that OXR1 was a direct target of hsa‑miR‑302e. Furthermore, the overexpression of OXR1 abolished the effect of sevoflurane on neuronal cells. The results of the present study indicated that sevoflurane exerts its neurotoxic effect by regulating the hsa‑miR‑302e/OXR1 axis. Therefore, the manipulation of the hsa‑miR‑302e/OXR1 pathway will be useful for preventing sevoflurane‑induced neurotoxicity.

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Identification of miRNAs Involved in the Protective Effect of Sevoflurane Preconditioning Against Hypoxic Injury in PC12 Cells

Cited by 17 publications

References 30 publications

Non-coding RNAs and neuroprotection after acute CNS injuries

Non-coding RNAs and neuroprotection after acute CNS injuries

Retracted: Deletion of long noncoding RNA EFNA3 aggravates hypoxia‐induced injury in PC‐12 cells by upregulation of miR‐101a

Sevoflurane‑induced neurotoxicity is driven by OXR1 post‑transcriptional downregulation involving hsa‑miR‑302e

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