Chronic Regulation of miR-124-3p in the Perilesional Cortex after Experimental and Human TBI

Vuokila, Niina; Aronica, Eleonora; Korotkov, A.; Vliet, Erwin A. van; Nuzhat, Salma; Puhakka, Noora; Pitkänen, Asla

doi:10.3390/ijms21072418

Cited by 23 publications

(22 citation statements)

References 104 publications

(139 reference statements)

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“…For example, canonical STaT3 signaling is associated with JaK-STaT signaling, whereby STaT3 is phosphorylated on tyrosine 750 (Y750), facilitating STaT3 homodimerization, nuclear translation, dna binding and initiation of transcription (42) activity in various cells. certain studies have reported the axis of mir-124-3p/STaT3 (47)(48)(49), but to the best of our knowledge, no previous study has focused on the functions of STaT3 in ec proliferation. inhibition of the STaT3 signaling pathway impairs angiogenesis and perfusion recovery in the muscles of patients with Pad (50).…”

Section: Discussionmentioning

confidence: 99%

miR‑124‑3p regulates angiogenesis in peripheral arterial disease by targeting STAT3

Shi

Luan

et al. 2020

Mol Med Rep

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Peripheral arterial disease (Pad) is the third leading cause of cardiovascular morbidity worldwide, after coronary artery disease and stroke. as endogenous regulators of gene expression, micrornas (mirs) are implicated in the development and progression of various diseases, including types of cancer, autoimmune diseases and heart diseases. in the present study, the role of mir-124-3p in Pad was investigated. The reverse transcription-quantitative Pcr results indicated that the expression levels of mir-124-3p were significantly increased in the ischemic tissue of the hindlimb ischemia (Hli) model and in hypoxic human umbilical vein endothelial cells compared with the corresponding control groups. Proliferation, wound healing and tube formation assays demonstrated the inhibition of mir-124-3p on angiogenesis in vitro and the Hli model indicated the same function of mir-124-3p in vivo. a dual-luciferase reporter revealed STaT3 as the target of mir-124-3p. The expression levels of mir-124-3p in human blood were negatively correlated with ankle-brachial index, which is an index for the evaluation of the severity of Pad. collectively, the present study indicated that mir-124-3p was a critical regulator of angiogenesis in Pad, and a potential diagnostic, prognostic and therapeutic target for Pad.

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Section: Discussionmentioning

confidence: 99%

miR‑124‑3p regulates angiogenesis in peripheral arterial disease by targeting STAT3

Shi

Luan

et al. 2020

Mol Med Rep

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“…The remaining 88 records were then manually screened and assessed for eligibility against the selection criteria previously described ( Section 2.2 ). Seventy-eight results were excluded during this process, leaving 10 miRNA studies for inclusion in the systematic review [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Figure 1 provides an overview of the miRNA literature search and study selection process.…”

Section: Resultsmentioning

confidence: 99%

“…The injury model, time point of analysis post-TBI and analysis method differed across the studies. Supplementary Materials Tables S1 and S2 provide an overview of the study characteristics for the included papers [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ]. The data collected here allowed us to establish whether performance of a meta-analysis was possible.…”

Section: Resultsmentioning

confidence: 99%

Co-Expression Network Analysis of MicroRNAs and Proteins in Severe Traumatic Brain Injury: A Systematic Review

Osgood

Ahmed

Pietro

2021

Cells

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Traumatic brain injury (TBI) represents one of the leading causes of mortality and morbidity worldwide, placing an enormous socioeconomic burden on healthcare services and communities around the world. Survivors of TBI can experience complications ranging from temporary neurological and psychosocial problems to long-term, severe disability and neurodegenerative disease. The current lack of therapeutic agents able to mitigate the effects of secondary brain injury highlights the urgent need for novel target discovery. This study comprises two independent systematic reviews, investigating both microRNA (miRNA) and proteomic expression in rat models of severe TBI (sTBI). The results were combined to perform integrated miRNA-protein co-expression analyses with the aim of uncovering the potential roles of miRNAs in sTBI and to ultimately identify new targets for therapy. Thirty-four studies were included in total. Bioinformatic analysis was performed to identify any miRNA–protein associations. Endocytosis and TNF signalling pathways were highlighted as common pathways involving both miRNAs and proteins found to be differentially expressed in rat brain tissue following sTBI, suggesting efforts to find novel therapeutic targets that should be focused here. Further high-quality investigations are required to ascertain the involvement of these pathways and their miRNAs in the pathogenesis of TBI and other CNS diseases and to therefore uncover those targets with the greatest therapeutic potential.

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“…11 Hybridization was performed using a 5 nM double-digoxigenin (DIG) (3 0 and 5 0 )-LNA probe for a 134-inhibitor probe (Exiqon) or an LNA-DIG scramble inhibitor probe. The cellular uptake mean ratio was calculated as per the formula described by Vuokila et al 47 for each region of interest (ROI). Sections for immunohistochemistry were incubated with primary antibody (NeuN, GFAP, Iba-1, or parvalbumin; all from Cell Signaling Technology) and fluorescently labeled secondary antibodies (Alexa Fluor 488 or 546).…”

Section: Reactome Pathway Enrichment Analysismentioning

confidence: 99%

Systemic delivery of antagomirs during blood-brain barrier disruption is disease-modifying in experimental epilepsy

et al. 2021

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Oligonucleotide therapies offer precision treatments for a variety of neurological diseases, including epilepsy, but their deployment is hampered by the blood-brain barrier (BBB). Previous studies showed that intracerebroventricular injection of an antisense oligonucleotide (antagomir) targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in animal models of epilepsy. In this study, we used assays of serum protein and tracer extravasation to determine that BBB disruption occurring after status epilepticus in mice was sufficient to permit passage of systemically injected Ant-134 into the brain parenchyma. Intraperitoneal and intravenous injection of Ant-134 reached the hippocampus and blocked seizure-induced upregulation of miR-134. A single intraperitoneal injection of Ant-134 at 2 h after status epilepticus in mice resulted in potent suppression of spontaneous recurrent seizures, reaching a 99.5% reduction during recordings at 3 months. The duration of spontaneous seizures, when they occurred, was also reduced in Ant-134-treated mice. In vivo knockdown of LIM kinase-1 (Limk-1) increased seizure frequency in Ant-134-treated mice, implicating de-repression of Limk-1 in the antagomir mechanism. These studies indicate that systemic delivery of Ant-134 reaches the brain and produces long-lasting seizure-suppressive effects after systemic injection in mice when timed with BBB disruption and may be a clinically viable approach for this and other disease-modifying microRNA therapies.

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Chronic Regulation of miR-124-3p in the Perilesional Cortex after Experimental and Human TBI

Cited by 23 publications

References 104 publications

miR‑124‑3p regulates angiogenesis in peripheral arterial disease by targeting STAT3

miR‑124‑3p regulates angiogenesis in peripheral arterial disease by targeting STAT3

Co-Expression Network Analysis of MicroRNAs and Proteins in Severe Traumatic Brain Injury: A Systematic Review

Systemic delivery of antagomirs during blood-brain barrier disruption is disease-modifying in experimental epilepsy

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