scholarly journals Long Noncoding RNA Fos Downstream Transcript Is Developmentally Dispensable but Vital for Shaping the Poststroke Functional Outcome

Stroke ◽  
2021 ◽  
Author(s):  
Suresh L. Mehta ◽  
Anil K. Chokkalla ◽  
TaeHee Kim ◽  
Saivenkateshkomal Bathula ◽  
Bharath Chelluboina ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Rna Sequencing ◽  
Brain Damage ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Focal Ischemia ◽  
Developmental Expression ◽  
Lesion Volume ◽  
Sequencing Analysis ◽  
Ischemic Brain

Background and Purpose: Stroke induces the expression of several long noncoding RNAs in the brain. However, their functional significance in poststroke outcome is poorly understood. We recently observed that a brain-specific long noncoding RNA called Fos downstream transcript (FosDT) is induced rapidly in the rodent brain following focal ischemia. Using FosDT knockout rats, we presently evaluated the role of FosDT in poststroke brain damage. Methods: FosDT knockout rats were generated using CRISPR-Cas9 genome editing on a Sprague-Dawley background. Male and female FosDT −/− and FosDT +/+ cohorts were subjected to transient middle cerebral artery occlusion. Postischemic sensorimotor deficits were evaluated between days 1 and 7 and lesion volume on day 7 of reperfusion. The developmental expression profile of FosDT was determined with real-time polymerase chain reaction and mechanistic implications of FosDT in the ischemic brain were conducted with RNA-sequencing analysis and immunostaining of pathological markers. Results: FosDT expression is developmentally regulated, with the adult cerebral cortex showing significantly higher FosDT expression than neonates. FosDT −/− rats did not show any anomalies in growth and development, fertility, brain cytoarchitecture, and cerebral vasculature. However, when subjected to transient focal ischemia, FosDT −/− rats of both sexes showed enhanced sensorimotor recovery and reduced brain damage. RNA-sequencing analysis showed that improved poststroke functional outcome in FosDT −/− rats is partially associated with curtailed induction of inflammatory genes, reduced apoptosis, mitochondrial dysfunction, and oxidative stress. Conclusions: Our study shows that FosDT is developmentally dispensable, mechanistically important, and a functionally promising target to reduce ischemic brain damage and facilitate neurological recovery.

Abstract P835: Long Noncoding RNA FosDT is Developmentally Dispensable but Critical for Shaping the Therapeutic Post-Stroke Functional Outcome

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Suresh L Mehta ◽  
Kahlilia Morris-Blanco ◽  
Anil Kiran Chokkalla ◽  
Saivenkateshkomal Bathula ◽  
Taehee Kim ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Brain Damage ◽  
Noncoding Rna ◽  
Focal Ischemia ◽  
Stroke Outcome ◽  
Developmentally Regulated ◽  
Ischemic Brain ◽  
Post Stroke ◽  
Transient Focal Ischemia ◽  
Sensorimotor Recovery

Stroke induces the expression of several long noncoding RNAs (lncRNAs) in the brain. However, their functional significance in post-stroke outcome is poorly understood. We recently observed that a brain-specific lncRNA called Fos downstream transcript (FosDT) is induced rapidly in rodent brain following focal ischemia. We here show that FosDT expression is developmentally regulated with adults specifically display higher expression in the cerebral cortex than neonates. To understand its significance in ischemic brain damage, we developed FosDT knockout rats using CRISPR-Cas9 genome editing. We found that FosDT knockout rats did not show any anomalies in growth and development, fertility, brain cytoarchitecture and cerebral vasculature. However, when subjected to transient focal ischemia, FosDT knockout rats of both sexes showed enhanced sensorimotor recovery and reduced brain damage. To further understand the mechanistic implications of FosDT in the ischemic brain, we conducted RNA-seq analysis. The result showed that improved post-stroke functional outcome in FosDT knockout rats is partially associated with curtailed post-ischemic induction of inflammatory genes. When rats subjected to transient focal ischemia were treated with FosDT siRNA, there was significant neuroprotection and better functional outcome irrespective of sex and age. FosDT siRNA was efficacious when administered peripherally and also in a delayed manner. Thus, preventing FosDT activation is beneficial for the post-stroke outcome.

Knockdown of long noncoding RNA AC245100.4 inhibits the tumorigenesis of prostate cancer cells via the STAT3/NR4A3 axis

Epigenomics ◽  
2021 ◽  
Author(s):  
Chi Liu ◽  
Ping Lin ◽  
Jiabin Zhao ◽  
Hui Xie ◽  
Rou Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Rna Sequencing ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Transcriptional Repressor ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Prostate Cancer Cells ◽  
Rna Immunoprecipitation

Aim: To explore the role and mechanism of long noncoding RNA AC245100.4 and NR4A3 in prostate cancer (PCa). Methods: RNA-sequencing analysis was used to detect the downstream genes of AC245100.4. A series of gain- and loss-of-function approaches were used to investigate the roles of AC245100.4 and NR4A3. RNA immunoprecipitation was performed to examine the interaction between AC245100.4 and STAT3. Results: AC245100.4 was significantly upregulated in PCa cells and tissues. Knockdown of AC21500.4 significantly inhibited the tumorigenesis of PCa cells. Mechanistically, AC245100.4 deregulated the transcription of NR4A3 via increasing p-STAT3, which acted as a transcriptional repressor of NR4A3. Conclusion: Knockdown of lncRNA AC245100.4 inhibits the tumorigenesis of PCa cells via the STAT3/ NR4A3 axis.

scholarly journals Long noncoding RNA and mRNA profiling in cetuximab‐resistant colorectal cancer cells by RNA sequencing analysis

2019 ◽  
Vol 8 (4) ◽  
pp. 1641-1651 ◽  
Author(s):  
Changwen Jing ◽  
Rong Ma ◽  
Haixia Cao ◽  
Zhuo Wang ◽  
Siwen Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Rna Sequencing ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Sequencing Analysis ◽  
Mrna Profiling ◽  
Colorectal Cancer Cells

scholarly journals Protective Role for Type 4 Metabotropic Glutamate Receptors against Ischemic Brain Damage

2010 ◽  
Vol 31 (4) ◽  
pp. 1107-1118 ◽  
Author(s):  
Slavianka G Moyanova ◽  
Federica Mastroiacovo ◽  
Lidia V Kortenska ◽  
Rumiana G Mitreva ◽  
Erminia Fardone ◽  
...  
Keyword(s):  
Brain Damage ◽  
Metabotropic Glutamate Receptors ◽  
Infarct Volume ◽  
Focal Ischemia ◽  
Protective Role ◽  
Ischemic Brain Damage ◽  
Systemic Injection ◽  
Ischemic Brain ◽  
Metabotropic Glutamate ◽  
Transient Focal Ischemia

We examined the influence of type 4 metabotropic glutamate (mGlu4) receptors on ischemic brain damage using the permanent middle cerebral artery occlusion (MCAO) model in mice and the endothelin-1 (Et-1) model of transient focal ischemia in rats. Mice lacking mGlu4 receptors showed a 25% to 30% increase in infarct volume after MCAO as compared with wild-type littermates. In normal mice, systemic injection of the selective mGlu4 receptor enhancer, N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-caboxamide (PHCCC; 10 mg/kg, subcutaneous, administered once 30 minutes before MCAO), reduced the extent of ischemic brain damage by 35% to 45%. The drug was inactive in mGlu4 receptor knockout mice. In the Et-1 model, PHCCC administered only once 20 minutes after ischemia reduced the infarct volume to a larger extent in the caudate/putamen than in the cerebral cortex. Ischemic rats treated with PHCCC showed a faster recovery of neuronal function, as shown by electrocorticographic recording and by a battery of specific tests, which assess sensorimotor deficits. These data indicate that activation of mGlu4 receptors limit the development of brain damage after permanent or transient focal ischemia. These findings are promising because selective mGlu4 receptor enhancers are under clinical development for the treatment of Parkinson's disease and other central nervous system disorders.

Abstract W MP38: Apolipoprotein A-I (ApoA-I) Mimetic Peptide, D-4F, Regulates miRNA Expression and Improves Functional Outcome after Stroke in Diabetic Rats

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Ruizhuo Ning ◽  
Michael Chopp ◽  
Alex Zacharek ◽  
Tao Yan ◽  
Cynthia Roberts ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Mirna Expression ◽  
Target Gene ◽  
M2 Macrophage ◽  
Lesion Volume ◽  
Ischemic Brain ◽  
Mimetic Peptide ◽  
Hdl Function ◽  
Functional Benefit ◽  
Gene And Protein Expression

Introduction: Diabetes mellitus (DM) in patients is associated with low high-density lipoprotein cholesterol (HDL-C) and impairment of the anti-oxidative capacity of HDL-C. Several miRNAs have been identified as having a physiological role in tissues in which diabetes complications occur. D-4F is an economical ApoA-I mimetic peptide which increases HDL function. We therefore investigated the therapeutic effect and underlying mechanisms of D-4F treatment of stroke induced functional benefit effects in type one DM (T1DM) rats. Methods: T1DM was induced in Wistar rats by streptozotocin (60mg/kg, ip) .Subsequently they were subjected to embolic middle cerebral artery occlusion. D-4F (10 mg/kg i.p.) was administered at 2h, 24h and 48h after stroke. Functional outcomes, brain blood barrier (BBB) leakage and lesion volume were evaluated. Results: D-4F treatment of stroke in T1DM rats significantly decreased Evans Blue dye leakage (15.85±1.52 ng/mg vs contro: 30.57± 5.88 ng/mg) and significantly improved functional outcome compared to non-treatment T1DM-control. D-4F treatment significantly increased miR-124a and miR-181c, but decreased miR-200b expression in the ischemic brain. Using laser capture, D-4F also significantly increased ischemic brain endothelial cell miR-126 expression compared to non-treatment control. In addition, D-4F treatment significantly decreased miR-181c target gene tumor necrosis factor-a (TNF-a), and miR-124a target gene monocyte chemoattractant protein-1 (MCP1) expression. D-4F also decreased proinflammatory nuclear NFkB (26.07±3.17 vs 37.43±3.47), Toll-like receptor 4 (TLR4, 7.26±0.69 vs 10.5±1.2), matrix metalloproteinase 9 (MMP9, 0.16±0.04 vs 0.48±0.09) expression, and increased CD163 (M2 macrophage marker, 120.98±8.13 vs 85.02± 9.47) number compared to T1DM-MCAo control rats. Conclusion: D-4F treatment of stroke in T1DM rats regulates miRNA expression and their target gene and protein expression and induces anti-inflammatory effects and promotes M2 macrophage polarization which may contribute to D-4F decreased BBB leakage and induced functional benefit effects after stroke in T1DM rats.

Methods to Study Long Noncoding RNA Expression and Dynamics in Zebrafish Using RNA Sequencing

2019 ◽  
pp. 77-110
Author(s):  
Samatha Mathew ◽  
Ambily Sivadas ◽  
Paras Sehgal ◽  
Kriti Kaushik ◽  
Shamsudheen K. Vellarikkal ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Rna Expression
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