MicroRNA-30e-5p has an Integrated Role in the Regulation of the Innate Immune Response during Virus Infection and Systemic Lupus Erythematosus

Mishra, Richa; Bhattacharya, Sanjana; Rawat, Bhupendra Singh; Kumar, Ashish; Kumar, Akhilesh; Niraj, Kavita; Chande, Ajit; Gandhi, Puneet; Khetan, Dheeraj; Aggarwal, Amita; Sato, Seiichi; Tailor, Prafullakumar; Takaoka, Akinori; Kumar, Himanshu

doi:10.1016/j.isci.2020.101322

Cited by 31 publications

(25 citation statements)

References 49 publications

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“…They reported that miRNA‐16 level was upregulated in plasma samples and peripheral blood cells of rheumatoid arthritis patients, downregulated in plasma of patients with SLE, upregulated in peripheral blood cells, and not altered in plasma of patients with ankylosing spondylitis, but upregulated in peripheral blood cells 35‐38 . Also, in the study conducted with SLE patients, it was shown that miR‐30e‐5p may be involved in the pathogenesis of the disease by triggering the immune response, while it was shown that miR‐30b‐5p expression was downregulated in serum samples of patients with scleroderma 39,40 . In a study conducted with multiple sclerosis patients, it was explained that expressions of miR‐15a, miR‐15b, miR‐16, miR‐17, miR‐98, miR‐374a, and miR‐454 were downregulated in peripheral blood samples 41 .…”

Section: Discussionmentioning

confidence: 99%

Can altered colostrum miRNA expression profile after cesarean delivery be a risk factor for autoimmune diseases?

Yerlikaya

Onmaz

Altunhan

et al. 2021

American J Rep Immunol

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Problem The cesarean section (CS) rate has increased significantly in North America, Western Europe, and Latin America. However, it has been reported that the incidence of inflammatory and autoimmune diseases such as asthma and type 1 diabetes increased in parallel with CS in these countries. Our aim was to investigate the expression level of miRNAs associated with inflammatory response and autoimmune diseases in colostrum samples and contribute to elucidating the role of CS in the pathogenesis of immune system–related diseases. Method of study Colostrum samples were taken from voluntary mothers who had 40 normal and 50 cesarean births. miRNAs were extracted from colostrums and detected to miRNA expression profiling (eighty‐four miRNAs) by quantitative real‐time PCR with the Fluidigm integrated microfluidic circuit technology. Results There was a statistically significant change in the expression levels of 17 miRNAs in the colostrums of mothers who had normal and cesarean delivery (p < .05), and all of miRNAs were upregulated in the colostrums of mothers who have had cesarean delivery. Conclusion Our best knowledge is that the study we conducted was the first to investigate the effect of delivery method (CS or normal) on the miRNA profile of colostrum. Cesarean delivery is a potential risk factor for inflammatory and immune system–related diseases in children due to dysregulation in miRNA expression.

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Section: Discussionmentioning

confidence: 99%

Can altered colostrum miRNA expression profile after cesarean delivery be a risk factor for autoimmune diseases?

Yerlikaya

Onmaz

Altunhan

et al. 2021

American J Rep Immunol

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“…This is induced by HBV and other viral infections and targets multiple negative regulators of innate immune signaling, thus activating immune response. The inhibition of miR-30e in mouse models and also in SLE patients (for example with anti-HBV treatment) has significantly reduced type I IFN response [ 211 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

Viral Infections and Systemic Lupus Erythematosus: New Players in an Old Story

Quaglia

Merlotti

Andrea

et al. 2021

Viruses

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A causal link between viral infections and autoimmunity has been studied for a long time and the role of some viruses in the induction or exacerbation of systemic lupus erythematosus (SLE) in genetically predisposed patients has been proved. The strength of the association between different viral agents and SLE is variable. Epstein–Barr virus (EBV), parvovirus B19 (B19V), and human endogenous retroviruses (HERVs) are involved in SLE pathogenesis, whereas other viruses such as Cytomegalovirus (CMV) probably play a less prominent role. However, the mechanisms of viral–host interactions and the impact of viruses on disease course have yet to be elucidated. In addition to classical mechanisms of viral-triggered autoimmunity, such as molecular mimicry and epitope spreading, there has been a growing appreciation of the role of direct activation of innate response by viral nucleic acids and epigenetic modulation of interferon-related immune response. The latter is especially important for HERVs, which may represent the molecular link between environmental triggers and critical immune genes. Virus-specific proteins modulating interaction with the host immune system have been characterized especially for Epstein–Barr virus and explain immune evasion, persistent infection and self-reactive B-cell “immortalization”. Knowledge has also been expanding on key viral proteins of B19-V and CMV and their possible association with specific phenotypes such as antiphospholipid syndrome. This progress may pave the way to new therapeutic perspectives, including the use of known or new antiviral drugs, postviral immune response modulation and innate immunity inhibition. We herein describe the state-of-the-art knowledge on the role of viral infections in SLE, with a focus on their mechanisms of action and potential therapeutic targets.

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“…miR-NC1 was used as a control for the experiment. Furthermore, we scanned the 3’UTRs of SOCS1 and SOCS3 for RNA binding site for AGO2 protein, in CLIP database, which is a key component of the miRNA-mediated silencing known as RNA-induced silencing complex (RISC) and found that the miR-30e make stable complexes with the target genes ( Mishra et al., 2020 ). To validate, miR-30e and negative regulators transcripts (SOCS1 and SOCS3) interaction, AGO2 pull-down assay was performed as shown in schematic ( Figure 2E ) and found that introduction of miR-30e significantly enriches the transcript of SOCS1 and SOCS3 during L. mono.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA-30e-5p Regulates SOCS1 and SOCS3 During Bacterial Infection

Mishra

Krishnamoorthy

Kumar

2021

Front. Cell. Infect. Microbiol.

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Host innate immunity is the major player against continuous microbial infection. Various pathogenic bacteria adopt the strategies to evade the immunity and show resistance toward the various established therapies. Despite the advent of many antibiotics for bacterial infections, there is a substantial need for the host-directed therapies (HDTs) to combat the infection. HDTs are recently being adopted to be useful in eradicating intracellular bacterial infection. Changing the innate immune responses of the host cells alters pathogen’s ability to reside inside the cell. MicroRNAs are the small non-coding endogenous molecules and post-transcriptional regulators to target the 3’UTR of the messenger RNA. They are reported to modulate the host’s immune responses during bacterial infections. Exploiting microRNAs as a therapeutic candidate in HDTs upon bacterial infection is still in its infancy. Here, initially, we re-analyzed the publicly available transcriptomic dataset of macrophages, infected with different pathogenic bacteria and identified significant genes and microRNAs common to the differential infections. We thus identified and miR-30e-5p, to be upregulated in different bacterial infections which enhances innate immunity to combat bacterial replication by targeting key negative regulators such as SOCS1 and SOCS3 of innate immune signaling pathways. Therefore, we propose miR-30e-5p as one of the potential candidates to be considered for additional clinical validation toward HDTs.

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MicroRNA-30e-5p has an Integrated Role in the Regulation of the Innate Immune Response during Virus Infection and Systemic Lupus Erythematosus

Cited by 31 publications

References 49 publications

Can altered colostrum miRNA expression profile after cesarean delivery be a risk factor for autoimmune diseases?

Can altered colostrum miRNA expression profile after cesarean delivery be a risk factor for autoimmune diseases?

Viral Infections and Systemic Lupus Erythematosus: New Players in an Old Story

MicroRNA-30e-5p Regulates SOCS1 and SOCS3 During Bacterial Infection

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