Delivery of an miR155 inhibitor by anti-CD20 single-chain antibody into B cells reduces the acetylcholine receptor-specific autoantibodies and ameliorates experimental autoimmune myasthenia gravis

Wang, Y.-Z.; Tian, Feng; Yan, Mei; Zhang, J.-M.; Liu, Q.; Lu, Jun; Zhou, Wenbin; Yang, Huan; Li, J.

doi:10.1111/cei.12265

Cited by 30 publications

(22 citation statements)

References 72 publications

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“…However, there is increasing evidence to suggest that MG arises from the interaction of multiple genes. For instance, several members of the nuclear factor- (NF-) κ B signaling pathway work cooperatively to trigger an immune response in MG [ 13 ], and a recent study found that miR-155 was upregulated in MG patients, while suppressing miR-155 impaired NF- κ B signaling [ 14 ]. Since functionally connected pathways crosstalk through common sets of genes [ 15 ], identifying miRNAs and their target genes that are dysregulated in MG is critical for developing effective treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Detecting Key Genes Regulated by miRNAs in Dysfunctional Crosstalk Pathway of Myasthenia Gravis

Cao

Wang

Zhang

et al. 2015

BioMed Research International

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Myasthenia gravis (MG) is a neuromuscular autoimmune disorder resulting from autoantibodies attacking components of the neuromuscular junction. Recent studies have implicated the aberrant expression of microRNAs (miRNAs) in the pathogenesis of MG; however, the underlying mechanisms remain largely unknown. This study aimed to identify key genes regulated by miRNAs in MG. Six dysregulated pathways were identified through differentially expressed miRNAs and mRNAs in MG, and significant crosstalk was detected between five of these. Notably, crosstalk between the “synaptic long-term potentiation” pathway and four others was mediated by five genes involved in the MAPK signaling pathway. Furthermore, 14 key genes regulated by miRNAs were detected, of which six—MAPK1, RAF1, PGF, PDGFRA, EP300, and PPP1CC—mediated interactions between the dysregulated pathways. MAPK1 and RAF1 were responsible for most of this crosstalk (80%), likely reflecting their central roles in MG pathogenesis. In addition, most key genes were enriched in immune-related local areas that were strongly disordered in MG. These results provide new insight into the pathogenesis of MG and offer new potential targets for therapeutic intervention.

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Section: Introductionmentioning

confidence: 99%

Detecting Key Genes Regulated by miRNAs in Dysfunctional Crosstalk Pathway of Myasthenia Gravis

Cao

Wang

Zhang

et al. 2015

BioMed Research International

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“…miRNAs are also responsible for NS functionality, being implicated in translation, RNA metabolism, gene development and regulation [252]. Many NSDs such as Alzheimer's disease (AD), epilepsy, Parkinson's disease (PD), glioblastoma (GBM), multiple sclerosis (MS), and myasthenia gravis (MG) are caused in part by aberrant expressions and/or dysfunctions of miRNAs [251,[253][254][255][256][257].…”

Section: Mirnas In Nervous System Disordersmentioning

confidence: 99%

“…Also, miRNAs play important roles in the most lethal brain tumor (GBM) in cellular proliferation, apoptosis, invasion, angiogenesis and stemness [255]. In MS and MG, evidence indicates the implication of miR-132, miR-124, and miR-155 [257,260]. A brief summary of miRNAs implicated in neurologic disorders is provided in Table 4.…”

Section: Mirnas In Nervous System Disordersmentioning

confidence: 99%

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Condrat

Thompson

Barbu

et al. 2020

Cells

858

583

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MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.Biogenesis of miRNA begins in the nucleus, where the transcription of its precursor, primary miRNA or pri-miRNA takes place under the influence of RNA polymerases II and III [11,12]. The resulting molecule is a hairpin-like structure, which contains a loop at one end [11]. This primordial mi-RNA precursor that is usually made up of hundreds of nucleotides is then processed consecutively by two RNase III enzymes [13][14][15]. The first enzyme to act upon the pri-miRNA, which still resides in the nucleus, is called Drosha or DCGR8, and turns it into a new hairpin-like structure of approximately 70 nucleotides, the Precursor-miRNA or pre-miRNA. The latter is then transported to the cytoplasm, with the help of Exportin-5, where it is cleaved again by the Ago2/Dicer complex leading to the short, mature miRNA double strands [16].Further on, one of the strands, usually known as the guide strand, will be integrated into the RNA-induced silencing complex (RISC), while the other one, known as the passenger strand, is going to be degraded, even though in some occasions it has been found to be also functional [17]. In most cases, the strand that contains the less stable 5 end or a uracil at the beginning is more likely to be selected as the guide strand [18][19][20]. In those situations, where the passenger strand is not degraded and both get incorporated into the miRISC complex, the mature miRNA in the guide strand will be the dominant one [21,22].The main role of miRNA in the human body is gene regulation [23] by mediating the degradation of mRNA and also by regulating transcription and translation through canonical and non-canonical mechanisms [4]. The canonical mechanism means that the miRISC complex containing the miRNA guide strand is exerting its action by binding to the targ...

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“…They have demonstrated that AID is required for immunoglobulin gene diversifi cation in B lymphocytes, and it also promotes chromosomal translocations, suggesting that miR-155 can act as a tumor suppressor by reducing potentially oncogenic translocations generated by AID [ 58 ]. Wang et al have recently demonstrated that knockdown of miR-155 disrupts the B-cell-activating factor (BAFF)-R-related signaling pathway and reduces the translocation of nuclear factor (NF)-κB into the nucleus [ 59 ].…”

Section: Mir-155mentioning

confidence: 99%

Noncoding RNAs in Cancer Immunology

Liu

2016

Advances in Experimental Medicine and Biology

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Cancer immunology is the study of interaction between cancer cells and immune system by the application of immunology principle and theory. With the recent approval of several new drugs targeting immune checkpoints in cancer, cancer immunology has become a very attractive field of research and is thought to be the new hope to conquer cancer. This chapter introduces the aberrant expression and function of noncoding RNAs, mainly microRNAs and long noncoding RNAs, in tumor-infiltrating immune cells, and their significance in tumor immunity. It also illustrates how noncoding RNAs are shuttled between tumor cells and immune cells in tumor microenvironments via exosomes or other microvesicles to modulate tumor immunity.

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Delivery of an miR155 inhibitor by anti-CD20 single-chain antibody into B cells reduces the acetylcholine receptor-specific autoantibodies and ameliorates experimental autoimmune myasthenia gravis

Cited by 30 publications

References 72 publications

Detecting Key Genes Regulated by miRNAs in Dysfunctional Crosstalk Pathway of Myasthenia Gravis

Detecting Key Genes Regulated by miRNAs in Dysfunctional Crosstalk Pathway of Myasthenia Gravis

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Noncoding RNAs in Cancer Immunology

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