Non-Coding RNAs and Hereditary Hemorrhagic Telangiectasia

Cannavicci, Anthony; Zhang, Qiuwang; Kutryk, Michael J.B.

doi:10.3390/jcm9103333

Cited by 8 publications

(6 citation statements)

References 113 publications

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“…In addition, emerging evidence from the modulatory role of non-coding-RNA (ncRNA) fetuses has attracted attention to their potential as diagnostic biomarkers for liquid biopsies and therapeutic applications [1][2][3]. Based on their length, ncRNAs can be subdivided into two main categories: short ncRNAs (<200 nucleotides) and long ncRNAs (>200 nucleotides) [4][5][6]. Within short ncRNAs, circulating microRNAs, which are single-stranded RNAs that are approximately 22 nucleotides long, can be used as potential biomarkers for diagnosis, prognosis, and therapeutics in various diseases, but are also delivered for intracellular communications through EVs-encapsulated forms [7,8].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles as Novel Drug-Delivery Systems through Intracellular Communications

Matsuzaka

Yashiro

2022

Membranes

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Since it has been reported that extracellular vesicles (EVs) carry cargo using cell-to-cell comminication according to various in vivo situations, they are exprected to be applied as new drug-delivery systems (DDSs). In addition, non-coding RNAs, such as microRNAs (miRNAs), have attracted much attention as potential biomarkers in the encapsulated extracellular-vesicle (EV) form. EVs are bilayer-based lipids with heterogeneous populations of varying sizes and compositions. The EV-mediated transport of contents, which includes proteins, lipids, and nucleic acids, has attracted attention as a DDS through intracellular communication. Many reports have been made on the development of methods for introducing molecules into EVs and efficient methods for introducing them into target vesicles. In this review, we outline the possible molecular mechanisms by which miRNAs in exosomes participate in the post-transcriptional regulation of signaling pathways via cell–cell communication as novel DDSs, especially small EVs.

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Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles as Novel Drug-Delivery Systems through Intracellular Communications

Matsuzaka

Yashiro

2022

Membranes

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“…Long noncoding RNAs (lncRNAs) are noncoding RNAs that are more than 200 nucleotides long ( 11 ). Most transcripts produced by mammalian genome sequences are lncRNAs ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

LncRNA NCAL1 potentiates natural killer cell cytotoxicity through the Gab2-PI3K-AKT pathway

Niu

Chen

et al. 2022

Front. Immunol.

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Natural killer (NK) cells perform immune surveillance functions in tumors. The antitumor effects of NK cells are closely related to tumor occurrence and development. However, the molecular factors that determine NK cell antitumor activity remain to be characterized. In the present study, we identified a novel long noncoding RNA (lncRNA), NK cell activity-associated lncRNA 1 (NCAL1), and investigated its function in NK cells. NCAL1 was primarily located in NK cell nuclei, where it functioned by activating Gab2, a scaffold protein with an essential role in immune cells. Gab2 positively regulated the killing activity of NK cells. Mechanistically, NCAL1 upregulated Gab2 epigenetically by binding to the Gab2 promoter, which decreased methylation, recruited the transcription factor Sp1, and increased H3K4me3 and H3K27ac levels in the Gab2 promoter. Furthermore, NCAL1 enhanced the cytotoxicity of NK cells toward tumor cells through the Gab2-PI3K-AKT pathway. Thus, NCAL1 potentiates NK cell cytotoxicity and is a promising therapeutic target to improve NK cell therapy.

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“…We have previously reported reduced levels of miRs-28-5p and -361-3p in HHT patient peripheral blood mononuclear cells (PBMCs), as well as elevated levels of circulating miR-210 in HHT patients with pulmonary AVMs [24,25]. Various other studies have identified miRNA dysregulation in HHT, but miRNA research in HHT is limited and an exact pathogenic role of any one miRNA has yet to be fully elucidated [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-132-3p, Downregulated in Myeloid Angiogenic Cells from Hereditary Hemorrhagic Telangiectasia Patients, Is Enriched in the TGFβ and PI3K/AKT Signalling Pathways

Cannavicci

Zhang

Faughnan

et al. 2022

Genes

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Background. Hereditary hemorrhagic telangiectasia (HHT) is a rare, autosomal dominant genetic disorder characterized by life-threatening vascular dysplasia. Myeloid angiogenic cells (MACs), alternatively called early endothelial progenitor cells or circulating angiogenic cells, do not directly incorporate into developing blood vessels, but augment angiogenesis in a paracrine manner. MAC dysfunction has been reported in HHT. MicroRNAs (miRNAs) regulate cellular function by modulating gene expression post-transcriptionally. To date, the role of miRNAs in HHT MAC dysfunction has not been documented. Objective. The goal of this study was to comparatively profile miRNAs in HHT patient and control MACs to identify dysregulated miRNAs that may be responsible for the observed MAC dysfunction in HHT. Methodology/Results. Twenty-three dysregulated miRNAs (twenty-one upregulated and two downregulated) in HHT MACs were identified with a TaqMan miRNA microarray. Pathway enrichment analysis showed that the dysregulated miRNAs were significantly enriched in pathways involved in HHT pathogenesis, such as the transforming growth factor β (TGFβ), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), and Hippo signalling pathways. Furthermore, miR-132-3p was determined to be significantly reduced in HHT MACs compared with controls by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Bioinformatic analysis revealed that miR-132-3p is significantly enriched in the TGFβ and PI3K/AKT signalling pathways, targeting SMAD4, an effector of the TGFβ signalling pathway and RASA1, a negative regulator of the PI3K/AKT signalling pathway, respectively. Conclusion. MiRNA dysregulation, specifically reduced expression of miR-132-3p, in HHT MACs was identified. The dysregulated miRNAs are significantly enriched in the TGFβ, PI3K/AKT, and Hippo signalling pathways. These data suggest that alteration in miRNA expression may impair these pathways and contribute to MAC dysfunction in HHT.

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Non-Coding RNAs and Hereditary Hemorrhagic Telangiectasia

Cited by 8 publications

References 113 publications

Extracellular Vesicles as Novel Drug-Delivery Systems through Intracellular Communications

Extracellular Vesicles as Novel Drug-Delivery Systems through Intracellular Communications

LncRNA NCAL1 potentiates natural killer cell cytotoxicity through the Gab2-PI3K-AKT pathway

MicroRNA-132-3p, Downregulated in Myeloid Angiogenic Cells from Hereditary Hemorrhagic Telangiectasia Patients, Is Enriched in the TGFβ and PI3K/AKT Signalling Pathways

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