DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain

Irfan, Jahanzaib; Febrianto, Muhammad Rizki; Sharma, Anju; Rose, Thomas J.; Mahmudzade, Yasamin; Giovanni, Simone Di; Nagy, István; Torres-Pérez, Jose Vicente

doi:10.3390/ijms23020752

Cited by 10 publications

(7 citation statements)

References 164 publications

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“…The decrease of PV’s activity is not associated with a significantly diminished activity of the Pa, and thus we can presume the stress-response remains unaltered in the different genotypes and groups. Although this has not been assessed in the present study, a feasible association derived from the diminished activity of the PV observed in these Mecp2 -null mice and unrelated to stress-reactivity, could be the altered visceral and neuropathic pain responses ( Liang et al, 2020 ; Vigli et al, 2021 ; Irfan et al, 2022 ), which have been previously reported in heterozygous females ( Samaco et al, 2013 ). Similarly, altered pain perception, including visceral, has been documented in RTT ( Barney et al, 2015 ).…”

Section: Discussionmentioning

confidence: 73%

Early life stress exacerbates behavioural and neuronal alterations in adolescent male mice lacking methyl-CpG binding protein 2 (Mecp2)

Torres-Pérez

Martínez-Rodríguez

Forte

et al. 2022

Front. Behav. Neurosci.

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The methyl-CpG binding protein 2 gene (MECP2) encodes an epigenetic transcriptional regulator implicated in neuronal plasticity. Loss-of-function mutations in this gene are the primary cause of Rett syndrome and, to a lesser degree, of other neurodevelopmental disorders. Recently, we demonstrated that both Mecp2 haploinsuficiency and mild early life stress decrease anxiety-like behaviours and neuronal activation in brain areas controlling these responses in adolescent female mice. Here, we extend this work to males by using Mecp2-null and wild type adolescent mice subjected to maternal separation and their non-stressed controls. We assessed their behavioural responses in a battery of anxiety-provoking tests. Upon exposure to an elevated plus maze in aversive conditions, we evaluated changes in c-FOS expression in stress- and anxiety-related brain regions. In addition, we assessed the impact of maternal separation in neuronal maturation using doublecortin and reelin as surrogate markers. Mutant males showed reduced motor abilities, increased activation of the olfactory bulbs, probably due to breathing abnormalities, and decreased activation of the paraventricular thalamic nucleus, when compared to wild type mice. In addition, maternal separation increased the number of immature doublecortin-like neurons found in Mecp2-null animals. Moreover, this work shows for the first time that reelin is decreased in the mutant animals at the olfactory tubercle, piriform cortex and hippocampal dentate gyrus, an effect also associated to maternal separation. Taken together, our results suggest that maternal separation exacerbates some phenotypical alterations associated with lack of MeCP2 in adolescent males.

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Section: Discussionmentioning

confidence: 73%

Early life stress exacerbates behavioural and neuronal alterations in adolescent male mice lacking methyl-CpG binding protein 2 (Mecp2)

Torres-Pérez

Martínez-Rodríguez

Forte

et al. 2022

Front. Behav. Neurosci.

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“…Although there are some studies on epigenetics in RA, they are not systematic and do not deeply investigate the specific roles of different epigenetic regulators in RA 13,14 . Noncoding RNA and DNA demethylation are two main categories of epigenetic regulation 15–18 . In the current study, we found that three epigenetic regulators, miRNA‐22 (MIR22), ten‐eleven translocation methylcytosine dioxygenase 3 (TET3), and pseudogene MT‐RNR2 like 2 (MTRNR2L2), could simultaneously participate in the RA‐FLS–mediated inflammatory response.…”

Section: Introductionmentioning

confidence: 81%

“…13,14 Noncoding RNA and DNA demethylation are two main categories of epigenetic regulation. [15][16][17][18] In the current study, we found that three epigenetic regulators, miRNA-22 (MIR22), teneleven translocation methylcytosine dioxygenase 3 (TET3), and pseudogene MT-RNR2 like 2 (MTRNR2L2), could simultaneously participate in the RA-FLS-mediated inflammatory response.…”

Section: Introductionmentioning

confidence: 82%

Epigenetic Regulatory Axis MIR22‐TET3‐MTRNR2L2 Represses Fibroblast‐Like Synoviocyte–Mediated Inflammation in Rheumatoid Arthritis

Fang,

Huang,

Zhu

et al. 2024

Arthritis & Rheumatology

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ObjectiveThe specific role of fibroblast‐like synoviocytes (FLS) in the pathogenesis of rheumatoid arthritis (RA) is still not fully elucidated. This study aimed to explore the molecular mechanisms of epigenetic pathways, including three epigenetic factors, MIR22, TET3, and MTRNR2L2, in RA‐FLS.MethodsThe expression of MIR22, TET3 and MTRNR2L2 in the synovium of patients with RA and arthritic mice were determined by FISH, qPCR, IHC and western blot. Mir22‐/‐ and Tet3+/‐ mice were used to establish CAIA model. Mir22 angomir and Tet3 siRNA were used to illustrate the therapeutic effects on arthritis using CIA model. Bioinformatics, luciferase reporter assay, 5hmC dot blotting, ChIP‐qPCR and hMeDIP‐qPCR were conducted to show the direct repression of MIR22 on the TET3 and transcriptional activation of TET3 on MTRNR2L2.ResultsThe Mir22‐/‐ CAIA model and RA‐FLS‐related in vitro experiments demonstrated the inhibitory effect of MIR22 on inflammation. MIR22 can directly inhibit the translation of TET3 in RA‐FLS by binding to its 3′UTR in TET3. The Tet3+/‐ mice‐established CAIA model showed less severe symptoms of arthritis in vivo. In vitro experiments further confirmed the pro‐inflammatory effect of TET3 in RA. In addition, CIA model was used to validate the therapeutic effects of Mir22 angomir and Tet3 siRNA. Finally, TET3 exerts its pro‐inflammatory effect by promoting 5hmC production in the promoter of its target MTRNR2L2 in RA‐FLS.ConclusionThe key role of the MIR22‐TET3‐MTRNR2L2 pathway in RA‐FLS provided an experimental basis for further studies into the pathogenesis and related targets of RA from the perspective of FLS.

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“…However, microarrays use already known sequences, thus making them unsuitable for the discovery of novel ncRNAs. 23 , 24 …”

Section: Detection Methods Of Circulating Ncrnasmentioning

confidence: 99%

Circulating Non-Coding RNAs as Potential Diagnostic Biomarkers in Hepatocellular Carcinoma

Chen¹

2022

JHC

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Hepatocellular carcinoma (HCC) is currently the second leading cause of cancer-related deaths worldwide, with high morbidity and mortality. The clinical diagnosis of HCC mainly depends on imaging technology, such as ultrasound and computed tomography, and serum biomarkers, such as alpha-fetoprotein (AFP). However, HCC is still hard to diagnose at an early stage due to the low sensitivity of the above mentioned traditional methods. Typically, HCC is diagnosed at an advanced stage when limited treatment options are available. It is urgent to identify effective biomarkers for the early diagnosis of HCC. Increasing evidence uncovered ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), could be used in HCC diagnosis. The aim of this review is to summarize our understanding of circulating miRNAs, lncRNAs and circRNAs as fluid-based non-invasive biomarkers, and aiming at providing new insights into the diagnosis of HCC.

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DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain

Cited by 10 publications

References 164 publications

Early life stress exacerbates behavioural and neuronal alterations in adolescent male mice lacking methyl-CpG binding protein 2 (Mecp2)

Early life stress exacerbates behavioural and neuronal alterations in adolescent male mice lacking methyl-CpG binding protein 2 (Mecp2)

Epigenetic Regulatory Axis MIR22‐TET3‐MTRNR2L2 Represses Fibroblast‐Like Synoviocyte–Mediated Inflammation in Rheumatoid Arthritis

Circulating Non-Coding RNAs as Potential Diagnostic Biomarkers in Hepatocellular Carcinoma

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