The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

Mandolesi, Georgia; Rizzo, Francesca Romana; Balletta, Sara; Bassi, Mario Stampanoni; Gilio, Luana; Guadalupi, Livia; Nencini, Monica; Moscatelli, Alessandro; Ryan, Colleen P.; Licursi, Valerio; Dolcetti, Ettore; Musella, Alessandra; Gentile, Antonietta; Fresegna, Diego; Bullitta, Silvia; Caioli, Silvia; Vanni, Valentina; Sanna, Krizia; Bruno, Antonio; Buttari, Fabio; Castelli, Chiara; Presutti, Carlo; Santa, Francesca De; Finardi, Annamaria; Furlan, Roberto; Centonze, Diego; Vito, Francesca De

doi:10.3390/cells10020330

Cited by 29 publications

(24 citation statements)

References 78 publications

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“…Briefly, after the collection of CSF samples (0.5–2 ml), cellular elements were removed immediately by centrifugation (1300 rpm: 189 G‐force, 10 min) and supernatants were stored at −80°C. RNA extraction and qPCR experiments were performed as described in Mandolesi et al, 2021 33 . As endogenous reference for the ΔCt calculation (Ct miR‐142‐3p–Ct miR‐204‐5p), we used miR‐204‐5p.…”

Section: Methodsmentioning

confidence: 99%

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MiR‐142‐3p regulates synaptopathy‐driven disease progression in multiple sclerosis

Vito

Musella

Fresegna

et al. 2021

Neuropathology Appl Neurobio

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Aim We recently proposed miR‐142‐3p as a molecular player in inflammatory synaptopathy, a new pathogenic hallmark of multiple sclerosis (MS) and of its mouse model experimental autoimmune encephalomyelitis (EAE), that leads to neuronal loss independently of demyelination. MiR‐142‐3p seems to be unique among potential biomarker candidates in MS, since it is an inflammatory miRNA playing a dual role in the immune and central nervous systems. Here, we aimed to verify the impact of miR‐142‐3p circulating in the cerebrospinal fluid (CSF) of MS patients on clinical parameters, neuronal excitability and its potential interaction with disease modifying therapies (DMTs). Methods and Results In a cohort of 151 MS patients, we found positive correlations between CSF miR‐142‐3p levels and clinical progression, IL‐1β signalling as well as synaptic excitability measured by transcranial magnetic stimulation. Furthermore, therapy response of patients with ‘low miR‐142‐3p’ to dimethyl fumarate (DMF), an established disease‐modifying treatment (DMT), was superior to that of patients with ‘high miR‐142‐3p’ levels. Accordingly, the EAE clinical course of heterozygous miR‐142 mice was ameliorated by peripheral DMF treatment with a greater impact relative to their wild type littermates. In addition, a central protective effect of this drug was observed following intracerebroventricular and ex vivo acute treatments of EAE wild type mice, showing a rescue of miR‐142‐3p‐dependent glutamatergic alterations. By means of electrophysiology, molecular and biochemical analysis, we suggest miR‐142‐3p as a molecular target of DMF. Conclusion MiR‐142‐3p is a novel and potential negative prognostic CSF marker of MS and a promising tool for identifying personalised therapies.

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Section: Methodsmentioning

confidence: 99%

“…As endogenous reference for the ΔCt calculation (Ct miR‐142‐3p–Ct miR‐204‐5p), we used miR‐204‐5p. Low ΔCt‐values indicate high miR levels and data are presented as 2^(−ΔCt) 28,33 . All details are provided in the Supporting Information.…”

Section: Methodsmentioning

confidence: 99%

MiR‐142‐3p regulates synaptopathy‐driven disease progression in multiple sclerosis

Vito

Musella

Fresegna

et al. 2021

Neuropathology Appl Neurobio

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“…Let-7b-5p is a miRNA with a wide range of biological functions ( Mandolesi et al, 2021 ). It plays a very important role in cell migration and proliferation and in antitumor processes ( Babapoor et al, 2017 ; Wu et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Exosomes Secreted by Nucleus Pulposus Stem Cells Derived From Degenerative Intervertebral Disc Exacerbate Annulus Fibrosus Cell Degradation via Let-7b-5p

Yin

Song

Xiao

et al. 2022

Front. Mol. Biosci.

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The pathogenesis of intervertebral disc degeneration (IDD) is complex and remains unclear. Nucleus pulposus stem cells (NPSCs) and annulus fibrosus cells (AFCs) play a critical role in the maintenance of intervertebral disc structure and function. Exosome-mediated miRNAs regulate cell proliferation, differentiation, apoptosis, and degradation. However, it is not clear whether the degenerative intervertebral disc-derived nucleus pulposus stem cells (D-NPSCs) can regulate the function of AFCs by delivering exosomes. Here, we show that exosomes secreted by nucleus pulposus stem cells derived from degenerative intervertebral disc (D-DPSC-exo) can exacerbate AFC degeneration via inhibiting cell proliferation, migration, matrix synthesis, and promoting apoptosis. Specifically, let-7b-5p was highly expressed in D-DPSC-exo. Transfection of let-7b-5p mimic was found to promote apoptosis and inhibit proliferation migration and matrix synthesis of AFCs. In addition, transfection with let-7b-5p inhibitor caused the effect of D-DPSC-exo on AFCs to be reversed. Furthermore, we found that D-DPSC-exo and let-7b-5p inhibited IGF1R expression and blocked the activation of the PI3K–Akt pathway. Results suggested that NPSC-exo exacerbated cell degeneration of AFCs via let-7b-5p, accompanied by inhibition of IGF1R expression, and PI3K–Akt pathway activation. Therefore, insights from this work may provide a clue for targeted molecular therapy of intervertebral disc degeneration.

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“…Exosomal miR-15b-5p and miR-451a were differentially expressed in 25 RRMS patients compared with 11 controls [110]. let-7b-5p is negatively associated with inflammation and disease severity in MS [118]. Upregulation of both miR-326 and miR-26a in the relapsing phase of MS patients compared with remitting phase and healthy controls was observed [64].…”

Section: Microrna Biomarkersmentioning

confidence: 97%

MicroRNAs, Multiple Sclerosis, and Depression

Wang

2021

IJMS

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Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects the brain and spinal cord. There are several disease courses in MS including relapsing–remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). Up to 50% of MS patients experience depressive disorders. Major depression (MD) is a serious comorbidity of MS. Many dysfunctions including neuroinflammation, peripheral inflammation, gut dysbiosis, chronic oxidative and nitrosative stress, and neuroendocrine and mitochondrial abnormalities may contribute to the comorbidity between MS and MD. In addition to these actions, medical treatment and microRNA (miRNA) regulation may also be involved in the mechanisms of the comorbidity between MS and MD. In the study, I review many common miRNA biomarkers for both diseases. These common miRNA biomarkers may help further explore the association between MS and MD.

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The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

Cited by 29 publications

References 78 publications

MiR‐142‐3p regulates synaptopathy‐driven disease progression in multiple sclerosis

MiR‐142‐3p regulates synaptopathy‐driven disease progression in multiple sclerosis

Exosomes Secreted by Nucleus Pulposus Stem Cells Derived From Degenerative Intervertebral Disc Exacerbate Annulus Fibrosus Cell Degradation via Let-7b-5p

MicroRNAs, Multiple Sclerosis, and Depression

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