MicroRNA signature associated with treatment response in myasthenia gravis: A further step towards precision medicine

Cavalcante, Paola; Mizrachi, Tehila; Barzago, Claudia; Scandiffio, Letizia; Bortone, Federica; Bonanno, Silvia; Frangiamore, Rita; Mantegazza, Renato; Bernasconi, Pia; Brenner, Talma; Vaknin‐Dembinsky, Adi; Antozzi, Carlo

doi:10.1016/j.phrs.2019.104388

Cited by 17 publications

(14 citation statements)

References 50 publications

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“…Reduced miR-181c expression in the PBMCs of AChR+ MG patients also seems to correlate with elevated serum levels of the interleukins IL-7 and IL-17 (100). A recent study observed that AChR+ MG patients non-responsive to immunosuppressive treatment had lower levels of miR-323b-3p, miR-409-3p, and miR-485-3p and higher levels of miR-181d-5p and miR-340-3p in PBMCs compared to those MG patients responding to immunosuppression (101).…”

Section: Intracellular Mirnas In Mgmentioning

confidence: 90%

Circulating miRNAs as Potential Biomarkers in Myasthenia Gravis: Tools for Personalized Medicine

Sabre

Punga

2020

Front. Immunol.

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Myasthenia gravis (MG) is an autoimmune disease caused by antibodies which attack receptors at the neuromuscular junction. One of the main difficulties in predicting the clinical course of MG is the heterogeneity of the disease, where disease progression differs greatly depending on the subgroup that the patient is classified into. MG subgroups are classified according to: age of onset [early-onset MG (EOMG; onset ≤ 50 years) versus late-onset MG (LOMG; onset > 50 years]; the presence of a thymoma (thymoma-associated MG); antibody subtype [acetylcholine receptor antibody seropositive (AChR+) and muscle-specific tyrosine kinase antibody seropositive (MuSK+)]; as well as clinical subtypes (ocular versus generalized MG). The diagnostic tests for MG, such as antibody titers, neurophysiological tests, and objective clinical fatigue score, do not necessarily reflect disease progression. Hence, there is a great need for reliable objective biomarkers in MG to follow the disease course as well as the individualized response to therapy toward personalized medicine. In this regard, circulating microRNAs (miRNAs) have emerged as promising potential biomarkers due to their accessibility in body fluids and unique profiles in different diseases, including autoimmune disorders. Several studies on circulating miRNAs in MG subtypes have revealed specific miRNA profiles in patients' sera. In generalized AChR+ EOMG, miR-150-5p and miR-21-5p are the most elevated miRNAs, with lower levels observed upon treatment with immunosuppression and thymectomy. In AChR+ generalized LOMG, the miR-150-5p, miR-21-5p, and miR-30e-5p levels are elevated and decrease in accordance with the clinical response after immunosuppression. In ocular MG, higher levels of miR-30e-5p discriminate patients who will later generalize from those remaining ocular. In contrast, in MuSK+ MG, the levels of the let-7 miRNA family members are elevated. Studies of circulating miRNA profiles in Lrp4 or agrin antibody-seropositive MG are still lacking. This review summarizes the present knowledge of circulating miRNAs in different subgroups of MG.

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Section: Intracellular Mirnas In Mgmentioning

confidence: 90%

Circulating miRNAs as Potential Biomarkers in Myasthenia Gravis: Tools for Personalized Medicine

Sabre

Punga

2020

Front. Immunol.

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“…miR-150-5p decreased 24 months after thymectomy, providing new evidence and further support for miR-150-5p as a biomarker for MG (Molin et al, 2018). Cavalcante et al (2019) identified miR-323b-3p, miR-409-3p, and miR-485-3p as predictive biomarkers for the responsiveness of MG patients to immunosuppressive drugs. miR-181d-5p, miR-323b-3p, miR-340-3p miR-409-3p, and miR-485-3p have also been validated as drug efficacy biomarkers (Cavalcante et al, 2019).…”

Section: Mirnas As Biomarkers Of Mgmentioning

confidence: 61%

“…Cavalcante et al (2019) identified miR-323b-3p, miR-409-3p, and miR-485-3p as predictive biomarkers for the responsiveness of MG patients to immunosuppressive drugs. miR-181d-5p, miR-323b-3p, miR-340-3p miR-409-3p, and miR-485-3p have also been validated as drug efficacy biomarkers (Cavalcante et al, 2019).…”

Section: Mirnas As Biomarkers Of Mgmentioning

confidence: 93%

Emerging Roles of Dysregulated MicroRNAs in Myasthenia Gravis

Wang

Zhang

2020

Front. Neurosci.

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Myasthenia gravis (MG) is a rare acquired autoimmune neuromuscular disease. Autoantibodies, cellular immunity, complement, and cytokines are involved in the pathogenesis of MG. It is characterized by the dysfunction of neuromuscular junction transmission and skeletal muscle weakness. MicroRNAs (miRNAs) are non-coding small molecule ribonucleic acids that regulate various biological processes (e.g., development, differentiation, and immunity) at the transcriptional and post-transcriptional levels of gene expression. miRNAs play an important regulatory role in the pathogenesis of autoimmune diseases, including MG. In recent studies, the functional mechanisms underlying the role of miRNAs in the pathogenesis of MG have received increasing attention. miRNAs are highly stable and have high specificity in peripheral body fluids. Therefore, the miRNAs in body fluids may represent promising biomarkers for determining the prognosis of MG and the efficacy of treatment. This article reviews the role of miRNAs in the pathogenesis of MG, highlights the potential of miRNAs as new biomarkers for the diagnosis of MG, and deepens our understanding of disease processes.

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“…The miRNA is a type of non-coding RNA transcribed by RNA Pol II. It can recognize and silence the expression of specific genes through specific sequences 49,50 . In the present work, miR-30c was identified as a kind of miR to enhance the sensitivity of TNBC cells to olaparib via PXR pathway.…”

Section: Discussionmentioning

confidence: 99%

FBI-1 enhanced the resistance of triple-negative breast cancer cells to chemotherapeutic agents via the miR-30c/PXR axis

Yang

Ren²,

Wang³

et al. 2020

Cell Death Dis

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The factor that binds to the inducer of short transcripts‐1 (FBI-1) is a transcription suppressor and an important proto‐oncogene that plays multiple roles in carcinogenesis and therapeutic resistance. In the present work, our results indicated that FBI-1 enhanced the resistance of triple-negative breast cancer (TNBC) cells to chemotherapeutic agents by repressing the expression of micoRNA-30c targeting the pregnane X receptor (PXR). The expression of FBI-1 was positively related to PXR and its downstream drug resistance-related genes in TNBC tissues. FBI-1 enhanced the expression of PXR and enhanced the activation of the PXR pathway. The miR-30c decreased the expression of PXR by targeting the 3′-UTR of PXR, and FBI-1 increased the expression of PXR by repressing miR-30c’s expression. Through the miR-30c/PXR axis, FBI-1 accelerated the clearance or elimination of antitumor agents in TNBC cells (the TNBC cell lines or the patients derived cells [PDCs]) and induced the resistance of cells to antitumor agents. Therefore, the results indicated that the miR-30c/PXR axis participates in the FBI-1-mediated drug-resistance of TNBC cells.

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MicroRNA signature associated with treatment response in myasthenia gravis: A further step towards precision medicine

Cited by 17 publications

References 50 publications

Circulating miRNAs as Potential Biomarkers in Myasthenia Gravis: Tools for Personalized Medicine

Circulating miRNAs as Potential Biomarkers in Myasthenia Gravis: Tools for Personalized Medicine

Emerging Roles of Dysregulated MicroRNAs in Myasthenia Gravis

FBI-1 enhanced the resistance of triple-negative breast cancer cells to chemotherapeutic agents via the miR-30c/PXR axis

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