miR-127-3p Is an Epigenetic Activator of Myofibroblast Senescence Situated within the MicroRNA-Enriched Dlk1-Dio3‒Imprinted Domain on Mouse Chromosome 12

Auler, Markus; Bergmeier, Vera; Georgieva, Veronika S.; Pitzler, Lena; Frie, Christian; Nüchel, Julian; Eckes, Beate; Hinz, Boris; Brachvogel, Bent

doi:10.1016/j.jid.2020.11.011

Cited by 13 publications

(9 citation statements)

References 33 publications

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“…Regarding mmu-miR-127-3p, it was recently demonstrated that this miR in mouse skin wounds triggered a prolonged cell cycle arrest with unique molecular hallmarks of senescence, including activation of senescence-associated β-galactosidase, increases in p53 and p21 levels, inhibition of lamin B1 and proliferation factors, and the production of senescence-associated inflammatory and extracellular matrix remodeling components [ 44 ]. Several studies have demonstrated that miR-127-3p plays a major antitumor role in various cancers [ 45 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Altered RNome expression in Murine Gastrocnemius Muscle following Exposure to Jararhagin, a Metalloproteinase from Bothrops jararaca Venom

Nascimento

Zychar

Pessôa

et al. 2022

Toxins

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Small RNAs (sRNAs) and microRNAs (miRNAs) are small endogenous noncoding single-stranded RNAs that regulate gene expression in eukaryotes. Experiments in mice and humans have revealed that a typical small RNA can affect the expression of a wide range of genes, implying that small RNAs function as global regulators. Here, we used small RNA deep sequencing to investigate how jararhagin, a metalloproteinase toxin produced from the venom of Bothrops jararaca, affected mmu-miRNAs expression in mice 2 hours (Jar 2hrs) and 24 hours (Jar 24hrs) after injection compared to PBS control. The findings revealed that seven mmu-miRNAs were substantially differentially expressed (p value (p (Corr) cut-off 0.05, fold change ≥ 2) at 2 hrs after jararhagin exposure and that the majority of them were upregulated when compared to PBS. In contrast to these findings, a comparison of Jar 24hrs vs. PBS 24hrs demonstrated that the majority of identified mmu-miRNAs were downregulated. Furthermore, the studies demonstrated that mmu-miRNAs can target the expression of several genes involved in the MAPK signaling pathway. The steady antithetical regulation of mmu-miRNAs may correlate with the expression of genes that trigger apoptosis via MAPK in the early stages, and this effect intensifies with time. The findings expand our understanding of the effects of jararhagin on local tissue lesions at the molecular level.

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Section: Discussionmentioning

confidence: 99%

Altered RNome expression in Murine Gastrocnemius Muscle following Exposure to Jararhagin, a Metalloproteinase from Bothrops jararaca Venom

Nascimento

Zychar

Pessôa

et al. 2022

Toxins

View full text Add to dashboard Cite

show abstract

“…Regarding the mmu-miR-127-3p, it was recently demonstrated that this miR in mouse skin wounds triggered a prolonged cell cycle arrest with unique molecular hallmarks of senescence, including activation of the senescence-associated -galactosidase, increase in p53 and p21 levels, inhibition of lamin B1, proliferation factors, and the production of senescence-associated inflammatory and extracellular matrixremodeling components. [44]. Several studies demonstrated miR-127-3p plays a major anti-tumor role in various cancers [45][46][47].…”

Section: Discussionmentioning

confidence: 99%

Altered RNome expression in Murine Gastrocnemius Muscle Following Exposure to Jararhagin, a Metalloproteinase from Bothrops Jararaca Venom

Nascimento¹,

Zychar²,

Pessôa³

et al. 2022

Preprint

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Small RNAs (sRNA) and microRNAs (miRNAs) are small endogenous noncoding single-stranded RNAs that regulate gene expression in eukaryotes. Experiments in mice and humans have revealed that a typical small RNA can affect the expression of a wide range of genes, implying that small RNAs function as global regulators. Here, we used small RNA deep sequencing to investigate at how jararhagin, a metalloproteinase toxin produced from the venom of Bothrops jararaca, affected mmu-miRs expression in mice 2 h and 24 h after injection. The findings revealed that seven mmu-miRs were substantially differentially expressed (p-value (p (Corr) cut-off 0.05, FC 2) at 2h after jararhagin exposure, and that the majority of them were upregulated when compared to PBS. In contrast to these findings, a comparison of Jar 24h vs PBS 24hrs demonstrated that the majority of identified mmu-miRs were downregulated. Furthermore, the studies demonstrated that mmu-miR can target the expression of several genes involved in the MAPK signaling pathway. The steady antithetical regulation of mmu-miRs may correlates with the expression of genes that trigger apoptosis via MAPK in the early stages, and this effect intensifies with time. The findings expand our understanding of the effects of jararhagin on local tissue lesions at the molecular level.

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“…and ultimately promote the expression of fibrosis-related genes. ncRNA in the MAPK Pathway miR-21 [87], miR-127-3p [88], miR-43 [23], miR-32-5p [89], miR-338-3p [90], miR-155 [91], miR-22 [92], miR-503 [78], lncRNA FENDRR [93], and circEP400 [94] can affect the activation of the MAPK signaling pathway and regulate the differentiation of fibroblasts into myofibroblasts. We found that most of these ncRNAs did not directly target molecules in the MAPK pathway but targeted some proteins regulating the MAPK signaling pathway, such as PDCD4, DUSP1, SPRY1, etc.…”

Section: Mapk Signaling Pathwaymentioning

confidence: 99%

Noncoding RNAs: Master Regulator of Fibroblast to Myofibroblast Transition in Fibrosis

Zhang

Zhou

Wen

et al. 2023

IJMS

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Myofibroblasts escape apoptosis and proliferate abnormally under pathological conditions, especially fibrosis; they synthesize and secrete a large amount of extracellular matrix (ECM), such as α-SMA and collagen, which leads to the distortion of organ parenchyma structure, an imbalance in collagen deposition and degradation, and the replacement of parenchymal cells by fibrous connective tissues. Fibroblast to myofibroblast transition (FMT) is considered to be the main source of myofibroblasts. Therefore, it is crucial to explore the influencing factors regulating the process of FMT for the prevention, treatment, and diagnosis of FMT-related diseases. In recent years, non-coding RNAs, including microRNA, long non-coding RNAs, and circular RNAs, have attracted extensive attention from scientists due to their powerful regulatory functions, and they have been found to play a vital role in regulating FMT. In this review, we summarized ncRNAs which regulate FMT during fibrosis and found that they mainly regulated signaling pathways, including TGF-β/Smad, MAPK/P38/ERK/JNK, PI3K/AKT, and WNT/β-catenin. Furthermore, the expression of downstream transcription factors can be promoted or inhibited, indicating that ncRNAs have the potential to be a new therapeutic target for FMT-related diseases.

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miR-127-3p Is an Epigenetic Activator of Myofibroblast Senescence Situated within the MicroRNA-Enriched Dlk1-Dio3‒Imprinted Domain on Mouse Chromosome 12

Cited by 13 publications

References 33 publications

Altered RNome expression in Murine Gastrocnemius Muscle following Exposure to Jararhagin, a Metalloproteinase from Bothrops jararaca Venom

Altered RNome expression in Murine Gastrocnemius Muscle following Exposure to Jararhagin, a Metalloproteinase from Bothrops jararaca Venom

Altered RNome expression in Murine Gastrocnemius Muscle Following Exposure to Jararhagin, a Metalloproteinase from Bothrops Jararaca Venom

Noncoding RNAs: Master Regulator of Fibroblast to Myofibroblast Transition in Fibrosis

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