Altered Long Non-Coding RNA Transcriptomic Profiles in Ischemic Stroke

He, Wenzhuan; Wei, Dang; D, Cai; Chen, Siqia; Chen, Wenjie

doi:10.1089/hum.2017.064

Cited by 52 publications

(38 citation statements)

References 45 publications

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“…Studies have shown that ATP produced by glycolysis is vital for fast axonal transport of vesicles, synaptic ATP maintenance during energy stress, and energy requirement for action potential firing. 14,15 For example, the MEG3 expression is significantly elevated in focal cerebral ischemia mouse models and it mediates ischemic neuronal death in stroke by activating p53 or targeting the miR-21/PDCD4 signaling pathway. During ischemic attacks and acute glucose deprivation, glycolytic metabolism in the brain is impaired, leading to neuron death.…”

mentioning

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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mentioning

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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“…This analysis was conducted to provide functional implications of the candidate lncRNA ENSMUST00000160839 by analyzing its association with mRNAs. Although three biological replicates were used in co-expression analysis in previous studies [62][63][64][65], the increased sample size in the present study will help validate the results.…”

Section: Discussionmentioning

confidence: 67%

RNA-sequencing analysis reveals the potential contribution of lncRNAs in palmitic acid-induced insulin resistance of skeletal muscle cells

Han

You

et al. 2020

Bioscience Reports

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Insulin resistance (IR) has been considered as the common pathological basis and developmental driving force for most metabolic diseases. Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators in modulation of glucose and lipid metabolism. However, the comprehensive profile of lncRNAs in skeletal muscle cells under the insulin resistant status and the possible biological effects of them were not fully studied. In this research, using C2C12 myotubes as cell models in vitro, deep RNA-sequencing was performed to profile lncRNAs and mRNAs between palmitic acid-induced IR C2C12 myotubes and control ones. The results revealed that a total of 144 lncRNAs including 70 up-regulated and 74 down-regulated (|fold change| > 2, q < 0.05) were significantly differentially expressed in palmitic acid-induced insulin resistant cells. In addition, functional annotation analysis based on the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases revealed that the target genes of the differentially expressed lncRNAs were significantly enriched in fatty acid oxidation, lipid oxidation, PPAR signaling pathway, and insulin signaling pathway. Moreover, Via qPCR, most of selected lncRNAs in myotubes and db/db mice skeletal muscle showed the consistent expression trends with RNA-sequencing. Co-expression analysis also explicated the key lncRNA-mRNA interactions and pointed out a potential regulatory network of candidate lncRNA ENSMUST00000160839. In conclusion, the present study extended the skeletal muscle lncRNA database and provided novel potential regulators for future genetic and molecular studies on insulin resistance, which is helpful for prevention and treatment of the related metabolic diseases. sensitivity and whole-body metabolism. For example, perturbed heterogeneous nuclear ribonucleoprotein A1-induced turbulences in glucose homeostasis in the skeletal muscle could accelerate systemic IR under both basal and high-fat induced conditions [7]. Conversely, activating mTOR signaling, improved insulin sensitivity in the skeletal muscle, which could enhance whole-body metabolism via weight loss and an increased fatty acid oxidation capacity in the adipose tissue and liver [8,9]. Studies have shown that among the widely recognized mechanisms underlying IR in the skeletal muscle, quite a few studies displayed that accumulation of 'toxic' lipid metabolites was considered as an important contributor to IR in skeletal muscle [10][11][12][13][14]. Lipid-induced IR has been associated with different cellular events in skeletal muscle cells, including impaired insulin signaling transduction of IRS1-PI3K [15], activation of inflammatory and pro-inflammatory cytokines [16], abnormally accumulation of ceramides [17], and mitochondrial dysfunction [18]. Therefore, the factors or the mechanisms underlying IR in the skeletal muscle, which are induced by lipid overload, must be explored.Long noncoding RNAs (lncRNAs), transcribed by RNA polymerase II, is a kind of RNA molecules with lengths of more than 200 nucleot...

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“…Further, the functional variant rs139365823 in pre-miR-138 enhanced the miR-138-mediated inhibitory regulation of DVL2 and conferred the risk for congenital heart disease in a Chinese population [38]. LncRNA LINC00884 was one of the top five lncRNAs with the largest numbers of ICM associations in the study of He et al [39].…”

Section: Icm Susceptibility Biomarkersmentioning

confidence: 91%

A susceptibility biomarker identification strategy based on significantly differentially expressed ceRNA triplets for ischemic cardiomyopathy

et al. 2020

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Ischemic cardiomyopathy (ICM) is a common human heart disease that causes death. No effective biomarkers for ICM could be found in existing databases, which is detrimental to the in-depth study of this disease. In the present study, ICM susceptibility biomarkers were identified using a proposed strategy based on RNA-Seq and miRNA-Seq data of ICM and normal samples. Significantly differentially expressed competing endogenous RNA (ceRNA) triplets were constructed using permutation tests and differentially expressed mRNAs, miRNAs and lncRNAs. Candidate ICM susceptible genes were screened out as differentially expressed genes in significantly differentially expressed ceRNA triplets enriched in ICM-related functional classes. Finally, eight ICM susceptibility genes and their significantly correlated lncRNAs with high classification accuracy were identified as ICM susceptibility biomarkers. These biomarkers would contribute to the diagnosis and treatment of ICM. The proposed strategy could be extended to other complex diseases without disease biomarkers in public databases.

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Altered Long Non-Coding RNA Transcriptomic Profiles in Ischemic Stroke

Cited by 52 publications

References 45 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

RNA-sequencing analysis reveals the potential contribution of lncRNAs in palmitic acid-induced insulin resistance of skeletal muscle cells

A susceptibility biomarker identification strategy based on significantly differentially expressed ceRNA triplets for ischemic cardiomyopathy

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