Dysregulation of long non-coding RNA profile in peripheral blood of multiple sclerosis patients

Dastmalchi, Romina; Ghafouri‐Fard, Soudeh; Omrani, Mir Davood; Mazdeh, Mehrdokht; Sayad, Arezou

doi:10.1016/j.msard.2018.07.044

Cited by 51 publications

(40 citation statements)

References 21 publications

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“…The expression of NEAT1 is upregulated in numerous human malignancies including prostate, lung, and breast cancers, and glioblastoma 42,54-56. Previous studies have shown that NEAT1 can regulate the immune response in systemic lupus erythematosus (SLE), multiple sclerosis, and viral infections 20,21,57. Imamura et al have shown that NEAT1 can activate transcription of the antiviral gene IL-8 by relocating SFPQ from the IL-8 promoter after infection with a virus 21.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of NEAT1 induces tolerogenic phenotype in dendritic cells by inhibiting activation of NLRP3 inflammasome

et al. 2019

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Rationale: Tolerogenic dendritic cells (tol-DCs) play essential roles in immune-related diseases and induce immune tolerance by shaping T-cell responses. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play important regulatory roles in the immune system. However, the potential roles and underlying mechanisms of lncRNAs in tol-DCs remain unclear. Methods: RNA in-situ hybridization, histochemistry, and qRT-PCR were performed to determine the distribution and expression of NEAT1 in DCs. Flow cytometry was used to analyze the tolerogenic function of DCs. Small sequencing, followed by bioinformatic analysis, was performed to determine the target genes of NEAT1. The mechanism of NEAT1 was explored using a luciferase reporter, chromatin immunoprecipitation assays, and Immunofluorescence. In-vivo experiments were used to investigate the induction of immune tolerance via NEAT1-knockdown DCs. Results: Our results show that lncRNA NEAT1 can induce tolerogenic phenotype in DCs. Mechanistically, small RNA-seq analysis revealed that NEAT1 knockdown preferentially affected the expression of miR-3076-3p. Furthermore, NEAT1 used the NLRP3 inflammasome as a molecular decoy for miR-3076-3p, thus facilitating the expression of tolerogenic phenotype in DCs. Moreover, the transcription factor E2F1 acted as a repressor of NEAT1 transcription via activity of H3K27ac. Our results also indicate that NEAT1 knockdown in DCs can induce immune tolerance in models of experimental autoimmune myocarditis and heart transplantation. Conclusions: Taken together, our study shows the mechanism used by NEAT1 in inducing tol-DCs and highlights the therapeutic potential of targeting NEAT1 for the treatment of immune-related diseases.

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Section: Discussionmentioning

confidence: 99%

Knockdown of NEAT1 induces tolerogenic phenotype in dendritic cells by inhibiting activation of NLRP3 inflammasome

et al. 2019

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“…Few studies showed that dysregulated expression of lncRNAs profiles within CNS lesions has a big role in pathogenesis of MS [4,9,31]. There is an interest in studying lncRNAs biomarkers to predict their role in disease activity, progression and treatment response.…”

Section: Discussionmentioning

confidence: 99%

“…It was found that lncRNAs may have a crucial role in autoimmune diseases through activation, differentiation and imbalanced expression of immune cells (T cells, B cells, macrophages and NK cells) that have been observed in diseases of autoimmunity such as psoriasis, rheumatoid arthritis and systemic lupus erythematous (SLE) [8]. It is interesting that some lncRNAs were discovered to be dysregulated in peripheral blood mononuclear cells in MS patients suggesting their role in the pathogenesis of MS [9].…”

Section: Introductionmentioning

confidence: 99%

LncRNAs, MALAT1 and lnc-DC as potential biomarkers for multiple sclerosis diagnosis

et al. 2019

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Long non-coding RNAs (lncRNAs) play an important role in gene regulation and show greater tissue specificity and complexity of biological functions. There is on-going research in their contribution in autoimmune diseases like multiple sclerosis (MS). Our study aimed at the evaluation of serum levels of lncRNAs, MALAT1 and lnc-DC in MS patients and the investigation of the association between these lncRNAs and the disease activity. Serum from 45 MS patients and 45 healthy controls was separated. MALAT1 and lnc-DC expression levels were assayed by qRT-PCR. MALAT1 and lnc-DC were significantly increased in MS patients (P=0.004 and P=0.006, respectively) in comparison with controls. There was a significant increase in expression of MALAT1 in secondary progressive MS (SPMS) subgroup compared with controls (P<0.0001); however, significant elevation of lnc-DC was demonstrated in relapsing remitting MS (RRMS) subtype (P=0.003) compared with normal controls. A positive association between the expression levels of MALAT1 and lnc-DC (r = 0.513, P < 0.0001) in MS patients was detected. Moreover, positive correlation was observed between MALAT1and lnc-DC in RRMS (r = 0.569, P = 0.001). Serum levels of MALAT1 and lnc-DC may serve as potential novel molecular biomarkers for MS diagnosis and may provide a new direction for its treatment.

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“…In the present study, we assessed the expression levels of PANDA in three types of bladder tissues including normal, ANCT and tumour tissues and found no significant difference in its expression between these three sets of samples. This lncRNA has been suggested to be involved in a variety of human disorders including neuroinflammatory and malignant conditions [6,13]. tumour tissues and normal tissues (expression ratio 2.72, P = 0.57) (Graph 1).…”

Section: Gene Namementioning

confidence: 99%

P21-Associated ncRNA DNA Damage-Activated Expression in Bladder Cancer

et al. 2019

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Background: Long non-coding RNAs (lncRNA) have recently been the focus of attention of cancer researchers due to their diverse roles in the carcinogenesis process. These transcripts regulate critical steps in the normal cellular processes, so dysregulation of their expression participate in the pathogenesis of several cancers. P21-associated ncRNA DNA damage activated (PANDA) has a special situation in this regard due to its adjacency to the CDKN1A locus. It is involved in the regulation of DNA damage response as well as cell senescence and proliferation. Material and methods: In the current study, we assessed the expression of this lncRNA in bladder cancer tissue, adjacent non--cancerous tissues (ANCTs) and normal bladder samples by means of quantitative real time PCR method. Results: No significant difference has been detected in PANDA expression either between tumour tissue and ANCTs (expression ratio 1.75, P = 0.11) or between tumour tissue and normal tissues (expression ratio 2.72, P = 0.57). The expression level of this lncRNA was not associated with any of the demographic or clinical data of patients such as tumor grade or recurrence or cancer-associated risk factors such as cigarette smoking or opium addiction. Conclusion: Consequently, the current study implies that PANDA is not involved in the pathogenesis of bladder cancer. Assessment of expression of other lncRNAs would help in identification of bio markers for this cancer.

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Dysregulation of long non-coding RNA profile in peripheral blood of multiple sclerosis patients

Cited by 51 publications

References 21 publications

Knockdown of NEAT1 induces tolerogenic phenotype in dendritic cells by inhibiting activation of NLRP3 inflammasome

Knockdown of NEAT1 induces tolerogenic phenotype in dendritic cells by inhibiting activation of NLRP3 inflammasome

LncRNAs, MALAT1 and lnc-DC as potential biomarkers for multiple sclerosis diagnosis

P21-Associated ncRNA DNA Damage-Activated Expression in Bladder Cancer

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