Deep Sequencing of Small RNAs in Blood of Patients with Brain Arteriovenous Malformations

Chen, Yong; Li, Zhili; Shi, Yi; Huang, Gui Chao; Chen, Longyi; Tan, Haibin; Wang, Zhenyu; Chen, Yin; Hu, Junting

doi:10.1016/j.wneu.2018.04.097

Cited by 19 publications

(21 citation statements)

References 44 publications

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“…It is also apparent that its inhibition via the lcnRNA H19 escalates the angiogenic potency of mesenchymal stem cells (MSCs) concomitantly while increasing VEGF-A expression [104]. As reported by Chen et al, miR-199a-5p was consistently upregulated in the serum of BAVM patients, acting via the VEGF pathway [18]. This miRNA can also be utilized as a biomarker for brain AVMs, along with miR-7-5p and miR-200b-3p.…”

Section: Mir-199a-5pmentioning

confidence: 83%

“…Despite the fact that little is known of the implications miR-7-5p has in the development of BAVMs, Chen et al established that it was significantly upregulated in the serum of patients with these malformations [18]. According to them, the Vascular Endothelial Growth Factor (VEGF) signaling pathway is implicated in 15 of the genes targeted by miR-7-5p, among miR-199a-5p and miR-200b-3p.…”

Section: Mir-7-5pmentioning

confidence: 99%

“…MicroRNAs (miRNA or miR) represent short strands of non-coding ribonucleic acid (RNA), approximately 20-22 nucleotides long, with the capacity to regulate the expression of target genes via the complete or partial binding onto their respective complementary sequences [17][18][19][20][21][22]. As a result, they hamper translation while also stimulating mRNA degradation.…”

Section: Introductionmentioning

confidence: 99%

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An Insight into the microRNAs Associated with Arteriovenous and Cavernous Malformations of the Brain

Florian

Buruiană

Şuşman

et al. 2021

Cells

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Background: Brain arteriovenous malformations (BAVMs) and cerebral cavernous malformations (CCMs) are rare developmental anomalies of the intracranial vasculature, with an irregular tendency to rupture, and as of yet incompletely deciphered pathophysiology. Because of their variety in location, morphology, and size, as well as unpredictable natural history, they represent a management challenge. MicroRNAs (miRNAs) are strands of non-coding RNA of around 20 nucleotides that are able to modulate the expression of target genes by binding completely or partially to their respective complementary sequences. Recent breakthroughs have been made on elucidating their contribution to BAVM and CCM occurrence, growth, and evolution; however, there are still countless gaps in our understanding of the mechanisms involved. Methods: We have searched the Medline (PubMed; PubMed Central) database for pertinent articles on miRNAs and their putative implications in BAVMs and CCMs. To this purpose, we employed various permutations of the terms and idioms: ‘arteriovenous malformation’, ‘AVM’, and ‘BAVM’, or ‘cavernous malformation’, ‘cavernoma’, and ‘cavernous angioma’ on the one hand; and ‘microRNA’, ‘miRNA’, and ‘miR’ on the other. Using cross-reference search; we then investigated additional articles concerning the individual miRNAs identified in other cerebral diseases. Results: Seven miRNAs were discovered to play a role in BAVMs, three of which were downregulated (miR-18a, miR-137, and miR-195*) and four upregulated (miR-7-5p, miR-199a-5p, miR-200b-3p, and let-7b-3p). Similarly, eight miRNAs were identified in CCM in humans and experimental animal models, two being upregulated (miR-27a and mmu-miR-3472a), and six downregulated (miR-125a, miR-361-5p, miR-370-3p, miR-181a-2-3p, miR-95-3p, and let-7b-3p). Conclusions: The following literature review endeavored to address the recent discoveries related to the various implications of miRNAs in the formation and growth of BAVMs and CCMs. Additionally, by presenting other cerebral pathologies correlated with these miRNAs, it aimed to emphasize the potential directions of upcoming research and biological therapies.

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Section: Mir-199a-5pmentioning

confidence: 83%

Section: Mir-7-5pmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An Insight into the microRNAs Associated with Arteriovenous and Cavernous Malformations of the Brain

Florian

Buruiană

Şuşman

et al. 2021

Cells

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“…Several methods can be used to identify and characterize miRNA mediated control of gene expression ( Calin et al, 2004 ; Krek et al, 2005 ; Grimson et al, 2007 ; Goff et al, 2009 ; Guerau-de-Arellano et al, 2012 ; Yoon et al, 2012 ; Ahmadi et al, 2013 ; Zheng et al, 2013 ; Agarwal et al, 2015 ; Dusl et al, 2015 ; Lagana, 2015 ; He et al, 2018 ). Expression levels of miRNAs can be estimated by deep-sequencing of samples from individuals diagnosed with a disease and healthy volunteers followed by statistical analyses ( Gombar et al, 2012 ; Gyvyte et al, 2017 ; Jin et al, 2017 ; Chen et al, 2018 ). Such an analysis does not provide direct mechanistic evidence for miRNA-gene association.…”

Section: Discussionmentioning

confidence: 99%

Further Evidence That MicroRNAs Can Play a Role in Hemophilia A Disease Manifestation: F8 Gene Downregulation by miR-19b-3p and miR-186-5p

Jankowska

McGill

Pezeshkpoor³

et al. 2020

Front. Cell Dev. Biol.

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Hemophilia A (HA) is a F8 gene mutational disorder resulting in deficiency or dysfunctional FVIII protein. However, surprisingly, in few cases, HA is manifested even without mutations in F8 . To understand this anomaly, we recently sequenced microRNAs (miRNAs) of two patients with mild and moderate HA with no F8 gene mutations and selected two highly expressing miRNAs, miR-374b-5p and miR-30c-5p, from the pool to explain the FVIII deficiency that could be mediated by miRNA-based F8 /FVIII suppression. In this report, an established orthogonal in vivo RNA-affinity purification approach was utilized to directly identify a group of F8 -interacting miRNAs and we tested them for F8 /FVIII suppression. From this pool, two miRNAs, miR-19b-3p and miR-186-5p, were found to be upregulated in a severe HA patient with a mutation in the F8 coding sequence and two HA patients without mutations in the F8 coding sequence were selected to demonstrate their role in F8 gene expression regulation in mammalian cells. Overall, these results provide further evidence for the hypothesis that by targeting the 3′UTR of F8 , miRNAs can modulate FVIII protein levels. This mechanism could either be the primary cause of HA in patients who lack F8 mutations or control the severity of the disease in patients with F8 mutations.

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“…These non-coding RNAs downregulates nicotinamide adenine dinucleotide phosphate (NADPH) reductase, lipoprotein lipase, etc., which may correlate with seizures in bAVM patients. Through deep sequencing of small RNAs in the blood of patients with bAVM, Chen et al found novel dysregulated miRNAs, one of which targets the VEGF signaling pathways [92]. It has been observed that miRNA-137 and miRNA-196* inhibit abnormal behavior of AVM smooth muscle cells in culture [93].…”

Section: Non-coding Rnamentioning

confidence: 99%

Recent Advances in Basic Research for Brain Arteriovenous Malformation

Prado

Han

et al. 2019

IJMS

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Arteriovenous malformations (AVMs) are abnormal connections of vessels that shunt blood directly from arteries into veins. Rupture of brain AVMs (bAVMs) can cause life-threatening intracranial bleeding. Even though the majority of bAVM cases are sporadic without a family history, some cases are familial. Most of the familial cases of bAVMs are associated with a genetic disorder called hereditary hemorrhagic telangiectasia (HHT). The mechanism of bAVM formation is not fully understood. The most important advances in bAVM basic science research is the identification of somatic mutations of genes in RAS-MAPK pathways. However, the mechanisms by which mutations of these genes lead to AVM formation are largely unknown. In this review, we summarized the latest advance in bAVM studies and discussed some pathways that play important roles in bAVM pathogenesis. We also discussed the therapeutic implications of these pathways.

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Deep Sequencing of Small RNAs in Blood of Patients with Brain Arteriovenous Malformations

Cited by 19 publications

References 44 publications

An Insight into the microRNAs Associated with Arteriovenous and Cavernous Malformations of the Brain

An Insight into the microRNAs Associated with Arteriovenous and Cavernous Malformations of the Brain

Further Evidence That MicroRNAs Can Play a Role in Hemophilia A Disease Manifestation: F8 Gene Downregulation by miR-19b-3p and miR-186-5p

Recent Advances in Basic Research for Brain Arteriovenous Malformation

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