MicroRNA Regulatory Network as Biomarkers of Late Seizure in Patients with Spontaneous Intracerebral Hemorrhage

Iwuchukwu, Ifeanyi; Nguyen, Doan; Beavers, Michelle; Tran, Vi; Sulaiman, Wale A. R.; Fannin, Erin S.; Lasseigne, Lindsay; Ramsay, Eugene; Wilson, Jason; Bazán, Nicolás G.

doi:10.1007/s12035-020-01872-y

Cited by 14 publications

(10 citation statements)

References 49 publications

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“…In another study, allelic variances of hsa-miR-5197 were found to be highly associated with non-small cell lung cancer (NSCLC) [50]. According to the Harvard and MD Anderson databases, miR-5197 shows significant differences between Caucasians and Chinese populations (data gained from a Han Chinese cohort from Nanjing, China) [50]. The rs2042253 polymorphism (T>C variation) of miR-5197 provided a protective effect on lung cancer survival.…”

Section: Mir-5197mentioning

confidence: 99%

The Prediction of miRNAs in SARS-CoV-2 Genomes: hsa-miR Databases Identify 7 Key miRs Linked to Host Responses and Virus Pathogenicity-Related KEGG Pathways Significant for Comorbidities

Arısan

Dart

Grant

et al. 2020

Viruses

102

165

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a member of the betacoronavirus family, which causes COVID-19 disease. SARS-CoV-2 pathogenicity in humans leads to increased mortality rates due to alterations of significant pathways, including some resulting in exacerbated inflammatory responses linked to the “cytokine storm” and extensive lung pathology, as well as being linked to a number of comorbidities. Our current study compared five SARS-CoV-2 sequences from different geographical regions to those from SARS, MERS and two cold viruses, OC43 and 229E, to identify the presence of miR-like sequences. We identified seven key miRs, which highlight considerable differences between the SARS-CoV-2 sequences, compared with the other viruses. The level of conservation between the five SARS-CoV-2 sequences was identical but poor compared with the other sequences, with SARS showing the highest degree of conservation. This decrease in similarity could result in reduced levels of transcriptional control, as well as a change in the physiological effect of the virus and associated host-pathogen responses. MERS and the milder symptom viruses showed greater differences and even significant sequence gaps. This divergence away from the SARS-CoV-2 sequences broadly mirrors the phylogenetic relationships obtained from the whole-genome alignments. Therefore, patterns of mutation, occurring during sequence divergence from the longer established human viruses to the more recent ones, may have led to the emergence of sequence motifs that can be related directly to the pathogenicity of SARS-CoV-2. Importantly, we identified 7 key-microRNAs (miRs 8066, 5197, 3611, 3934-3p, 1307-3p, 3691-3p, 1468-5p) with significant links to KEGG pathways linked to viral pathogenicity and host responses. According to Bioproject data (PRJNA615032), SARS-CoV-2 mediated transcriptomic alterations were similar to the target pathways of the selected 7 miRs identified in our study. This mechanism could have considerable significance in determining the symptom spectrum of future potential pandemics. KEGG pathway analysis revealed a number of critical pathways linked to the seven identified miRs that may provide insight into the interplay between the virus and comorbidities. Based on our reported findings, miRNAs may constitute potential and effective therapeutic approaches in COVID-19 and its pathological consequences.

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Section: Mir-5197mentioning

confidence: 99%

The Prediction of miRNAs in SARS-CoV-2 Genomes: hsa-miR Databases Identify 7 Key miRs Linked to Host Responses and Virus Pathogenicity-Related KEGG Pathways Significant for Comorbidities

Arısan

Dart

Grant

et al. 2020

Viruses

102

165

View full text Add to dashboard Cite

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“…The evaluation of intracerebral bleeding using the microRNA (miRNA) regulatory network as a potential biomarker for PSE confirmed that two miRNAs (4317 and 4315) are differentially expressed in PSE. The miRNA mi4317 regulates SCLC38A1, a glutamine-glutamate transporter [ 94 ]. The search for blood biomarkers that might be predictive for PSE confirmed known clinical risk factors, such as an NIHSS score of ≥ 8 ( p < 0.001) and ASS occurrence ( p < 0.001), and identified significant and independently associated serological markers, including an endostatin concentration > 1.23 ng/ml ( p = 0.046) and low concentrations of S100B and heat shock proteins (Hsp70 < 2.496 ng/ml, p = 0.006).…”

Section: Current Research Approachesmentioning

confidence: 99%

Seizures and epilepsy in patients with ischaemic stroke

Zöllner

Schmitt

Rosenow

et al. 2021

Neurol. Res. Pract.

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Background With the increased efficacy of stroke treatments, diagnosis and specific treatment needs of patients with post-stroke seizures (PSS) and post-stroke epilepsy have become increasingly important. PSS can complicate the diagnosis of a stroke and the treatment of stroke patients, and can worsen post-stroke morbidity. This narrative review considers current treatment guidelines, the specifics of antiseizure treatment in stroke patients as well as the state-of-the-art in clinical and imaging research of post-stroke epilepsy. Treatment of PSS needs to consider indications for antiseizure medication treatment as well as individual clinical and social factors. Furthermore, potential interactions between stroke and antiseizure treatments must be carefully considered. The relationship between acute recanalizing stroke therapy (intravenous thrombolysis and mechanical thrombectomy) and the emergence of PSS is currently the subject of an intensive discussion. In the subacute and chronic post-stroke phases, important specific interactions between necessary antiseizure and stroke treatments (anticoagulation, cardiac medication) need to be considered. Among all forms of prevention, primary prevention is currently the most intensively researched. This includes specifically the repurposing of drugs that were not originally developed for antiseizure properties, such as statins. PSS are presently the subject of extensive basic clinical research. Of specific interest are the role of post-stroke excitotoxicity and blood–brain barrier disruption for the emergence of PSS in the acute symptomatic as well as late (> 1 week after the stroke) periods. Current magnetic resonance imaging research focussing on glutamate excitotoxicity as well as diffusion-based estimation of blood–brain barrier integrity aim to elucidate the pathophysiology of seizures after stroke and the principles of epileptogenesis in structural epilepsy in general. These approaches may also reveal new imaging-based biomarkers for prediction of PSS and post-stroke epilepsy. Conclusion PSS require the performance of individual risk assessments, accounting for the potential effectiveness and side effects of antiseizure therapy. The use of intravenous thrombolysis and mechanical thrombectomy is not associated with an increased risk of PSS. Advances in stroke imaging may reveal biomarkers for PSS.

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“…Other studies have also recognized the important contribution of SLC38A1 as an amino acid transporter in placental and fetal development [42][43][44][45][46]. Similarly, research has already described the relationship of SLC38A1 with miR-150-5p, miR-593-3p, and miR-4317 in specific pathological conditions [47][48][49]. However, no study has reported the regulatory action of miR-373-3p on SLC38A1 until now.…”

Section: Discussionmentioning

confidence: 99%

miR-373-3p Regulates the Proliferative and Migratory Properties of Human HTR8 Cells via SLC38A1 Modulation

et al. 2022

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The genetic pathogenesis of selective intrauterine growth restriction (sIUGR) remains elusive, with evidence suggesting an important role of epigenetic factors such as microRNAs. In this study, we explored the relevance of miR-373-3p to the occurrence of sIUGR. Hypoxia enhanced the levels of miR-373-3p and hypoxia-inducible factor (HIF)-1α, while HIF-1α knockdown not only boosted the migration and proliferation of HTR8 cells but also suppressed the hypoxia-induced upregulation of miR-373-3p and SLC38A1. By contrast, HIF-1α overexpression induced miR-373-3p downregulation and SLC38A1 upregulation, reducing cell growth and migration, which could be reversed by a miR-373-3p inhibitor. Importantly, the miR-373-3p inhibitor and mimic reproduced phenomena similar to those induced by HIF-1α downregulation and overexpression, respectively (including altered SLC38A1 expression, mTOR activation, cell growth, and migration). Mechanistically, the miRNA regulated cell behaviors and related mTOR signaling by targeting SLC38A1 expression through an interaction with the 3 ′ -untranslated region of SLC38A1. The placental tissues of smaller sIUGR fetuses exhibited miR-373-3p and HIF-1α upregulation, SLC38A1 downregulation, and activated mTOR. Overall, miR-373-3p appears to restrict the growth and migration of HTR8 trophoblast cells by targeting SLC38A1, as observed in the placental tissues associated with smaller sIUGR fetuses, and it could have utility in the diagnosis and treatment of this disorder.

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MicroRNA Regulatory Network as Biomarkers of Late Seizure in Patients with Spontaneous Intracerebral Hemorrhage

Cited by 14 publications

References 49 publications

The Prediction of miRNAs in SARS-CoV-2 Genomes: hsa-miR Databases Identify 7 Key miRs Linked to Host Responses and Virus Pathogenicity-Related KEGG Pathways Significant for Comorbidities

The Prediction of miRNAs in SARS-CoV-2 Genomes: hsa-miR Databases Identify 7 Key miRs Linked to Host Responses and Virus Pathogenicity-Related KEGG Pathways Significant for Comorbidities

Seizures and epilepsy in patients with ischaemic stroke

miR-373-3p Regulates the Proliferative and Migratory Properties of Human HTR8 Cells via SLC38A1 Modulation

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