RTN1-C mediates cerebral ischemia/reperfusion injury via ER stress and mitochondria-associated apoptosis pathways

Gong, Lingli; Tang, Yuewen; An, Ran; Lin, Muya; Chen, Lijian; Du, Jian

doi:10.1038/cddis.2017.465

Cited by 181 publications

(122 citation statements)

References 58 publications

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“…Mechanisms such as apoptosis, oxidative stress, excitotoxicity, and inflammation cause neuronal cell death. [4][5][6] Blockage of the blood supply during ischemic stroke leads to reduced energy generation, followed by neuronal death. 7 Hence, it is urgent to target the glucose metabolism balance to improve neuron survival during the ischemic stroke.…”

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confidence: 99%

Long noncoding RNA HOTTIP alleviates oxygen‐glucose deprivation‐induced neuronal injury via modulating miR‐143/hexokinase 2 pathway

Wang

Zhao

et al. 2018

J of Cellular Biochemistry

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HOXA transcript at the distal tip (HOTTIP), which is a long noncoding RNA, plays an important role in multiple cancers and in coronary artery disease. Elevated microRNA-143 (miR-143) expression causes impaired glucose uptake that is responsible for the ischemic cerebral injury. However, the role and mechanism of HOTTIP in ischemic stroke are still unknown. The expression of HOTTIP and miR-143 was first detected in mouse models of transient middle cerebral artery occlusion and in primary neurons exposed to oxygen-glucose deprivation (OGD). We used gain-of function and loss-of function approaches in vitro to investigate the effect and mechanism of HOTTIP on ischemic stroke by evaluating cell viability, apoptosis, and glycolytic metabolism of neurons exposed to OGD. The HOTTIP expression was decreased, whereas miR-143 increased in experimental ischemic stroke models. Overexpression of HOTTIP by the pcDNA3.1-HOTTIP plasmid significantly increased cell viability, glucose uptake, and the expression of hexokinase 2 (HK-2) and pyruvate kinase M2 that were reduced by OGD insult. The HOTTIP overexpression also diminished OGD induced the apoptosis and the caspase-3 activity of neurons. The miR-143 mimic reversed these effects, and anti-miR-143 enhanced them. In addition, we found that HOTTIP could function as a competing endogenous RNA for miR-143 to modulate HK-2 expression. In conclusion, the HOTTIP expression was reduced in ischemic stroke. The HOTTIP overexpression attenuated OGD-induced neuronal injury and imbalanced glycolytic metabolism by sponging miR-143, resulting in the de-repression of its endogenous target HK-2. Taken together, these findings improve understanding of the pathogenesis of ischemic stroke.

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confidence: 99%

Long noncoding RNA HOTTIP alleviates oxygen‐glucose deprivation‐induced neuronal injury via modulating miR‐143/hexokinase 2 pathway

Wang

Zhao

et al. 2018

J of Cellular Biochemistry

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“…The last activity program (labeled Other) was characterized by high expression of the maternally expressed long non-coding RNA Meg3 42 and other genes that are associated with cerebral ischemic injury (e.g. Glg1 43 , Rtn1 44 ). Our functional interpretations of the novel activity programs are speculative, but they highlight the ability of cNMF to identify intriguing GEPs in an unbiased fashion.…”

Section: Cnmf Identifies Depolarization Induced and Novel Activity Prmentioning

confidence: 99%

Identifying Gene Expression Programs of Cell-type Identity and Cellular Activity with Single-Cell RNA-Seq

Kotliar

Veres

Nagy

et al. 2018

Preprint

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Identifying gene expression programs underlying cell-type identity and cellular processes is a crucial step toward understanding the organization of cells and tissues. Although single-cell RNA-Seq (scRNA-Seq) can quantify transcripts in individual cells, each cell's expression may derive both from programs determining cell-type and from programs facilitating dynamic cellular activities such as cell-division or apoptosis, which cannot be easily disentangled with current methods. Here, we introduce clustered nonnegative matrix factorization (cNMF) as a solution to this problem. We show with simulations that it deconvolutes scRNA-Seq profiles into interpretable programs corresponding to both cell-types and cellular activities. Applied to published brain organoid and visual cortex datasets, cNMF refines the hierarchy of cell-types and identifies both expected (e.g. cell-cycle and hypoxia) and intriguing novel activity programs. In summary, we show that cNMF can increase the accuracy of cell-type identification while simultaneously inferring interpretable cellular activity programs in scRNA-Seq data, thus providing useful insight into how cells vary dynamically within cell-types.. CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/310599 doi: bioRxiv preprint first posted online Apr. 30, 2018; 3 Main TextGenes act in concert to maintain a cell's identity as a specific cell-type, to respond to external signals, and to carry out complex cellular activities such as replication and differentiation. Coordinating the necessary genes for these functions is frequently achieved through transcriptional co-regulation, whereby genes are induced together as a gene expression program (GEP) in response to the appropriate internal or external signal 1,2 . Transcriptome-wide expression profiling technologies such as RNA-Seq have made it possible to conduct systematic and unbiased discovery of GEPs which, in turn, have shed light on the mechanisms underlying many cellular processes 3 .In traditional RNA-Seq, measurements are limited to an average expression profile of potentially dozens of cell-types in a tissue. Any observed changes in gene expression could reflect induction of a program in some specific cell-type(s), an average of many different changes in multiple cell-types, or changes in overall cell-type composition. The development of scRNA-Seq avoids this problem by measuring the expression of thousands of individual cells simultaneously. This permits determination of the cell-types in the sample as well as changes to any of their gene expression profiles. Exploiting this new technology, large-scale projects such as the Tabula Muris and the Human Cell Atlas are seeking to identify and characterize all the cell types in complex organisms in states of both health and disease 4,5 .Even with the ability to quantify e...

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“…Ischemic cerebrovascular disease remains one of the diseases with the highest morbidity, disability, and mortality in the world, which has also been a serious threat to the health and quality of life of the middle-aged and elderly people [1]. From the perspective of the pathogenesis involving ischemic injury, cerebral blood supply disorder is a crucial factor leading to ischemia, hypoxia, and focal ischemic necrosis of brain tissues.…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine had neuroprotective effects on hippocampal neuronal cells via targeting lncRNA SHNG16 mediated microRNA-10b-5p/BDNF axis

et al. 2020

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Dexmedetomidine (DEX), a highly selective alpha2 adrenergic receptor agonist, is a commonly used anesthetic drug in surgical procedures. Previous studies have indicated that DEX exerts neuroprotective effects while the detailed mechanism has not been fully elucidated. Here, we aim to study the role of lncRNA SHNG16 in DEX-induced brain protection and its underlying molecular mechanism. The rats underwent middle cerebral artery occlusion (MCAO) surgery and oxygen-glucose deprivation (OGD)-treated HT22 hippocampal neurons were treated with DEX, respectively. CCK8 was used to evaluate cell viability. sh-SHNG16 as well as miR-10b-5p mimics were transfected into hippocampal neurons to further explore the bio-function of SNHG16 and miR-10b-5p in vitro. Furthermore, the interactions between SHNG16 and miR-10b-5p, miR-10b-5p and BDNF gene were confirmed by dual-luciferase report assay. Our data revealed that DEX attenuated neurological damage of the MCAO rats and also increased the cell viability of the neurons significantly. Besides, expression of SHNG16 and BDNF were both downregulated while miR-10b-5p was upregulated in MCAO brain tissues or OGD treated neurons. DEX inhibited miR-10b-5p expression but increased SHNG16 and BDNF levels with a dosage effect. After transfection with sh-SHNG16 or miR-10b-5p mimics, the expression of BDNF protein was downregulated, accompanied with decreased neuron viability. Dual-luciferase assay showed that SHNG16 targeted on miR-10b-5p, which also could bind directly to the 3′-UTR sites of BDNF and negatively regulate its expression. In conclusion, DEX exerts neuroprotective in ischemic stroke via improving neuron damage, the underlying mechanism may be upregulating SHNG16 and BDNF via sponging miR-10b-5p.

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RTN1-C mediates cerebral ischemia/reperfusion injury via ER stress and mitochondria-associated apoptosis pathways

Cited by 181 publications

References 58 publications

Long noncoding RNA HOTTIP alleviates oxygen‐glucose deprivation‐induced neuronal injury via modulating miR‐143/hexokinase 2 pathway

Long noncoding RNA HOTTIP alleviates oxygen‐glucose deprivation‐induced neuronal injury via modulating miR‐143/hexokinase 2 pathway

Identifying Gene Expression Programs of Cell-type Identity and Cellular Activity with Single-Cell RNA-Seq

Dexmedetomidine had neuroprotective effects on hippocampal neuronal cells via targeting lncRNA SHNG16 mediated microRNA-10b-5p/BDNF axis

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