Long Non-coding RNA Peg13 Alleviates Hypoxic-Ischemic Brain Damage in Neonatal Mice via miR-20a-5p/XIAP Axis

Gao, Huan; Zhang, Yue; Xue, Huijing; Zhang, Qifei; Zhang, Yan; Shen, Yusi; Bing, Xiaosan

doi:10.1007/s11064-021-03474-z

Cited by 12 publications

(9 citation statements)

References 28 publications

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“…This experiment provided evidence against a cis -repressive role for Peg13 but additional experiments are merited, such as transcriptional inhibition by premature polyadenylation site insertion or CRISPRi. Separate from any potential cis -regulatory role, other recent work has proposed that Peg13 may act as a miRNA sponge ( Feng et al 2020 ; Jiang et al 2020 ; Gao et al 2022 ) and suppress Yy1 through the recruitment of the PRC2 complex ( Li et al 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Allelic chromatin structure precedes imprinted expression ofKcnk9during neurogenesis

Loftus,

Bae,

Whilden

et al. 2023

Genes Dev.

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Differences in chromatin state inherited from the parental gametes influence the regulation of maternal and paternal alleles in offspring. This phenomenon, known as genomic imprinting, results in genes preferentially transcribed from one parental allele. While local epigenetic factors such as DNA methylation are known to be important for the establishment of imprinted gene expression, less is known about the mechanisms by which differentially methylated regions (DMRs) lead to differences in allelic expression across broad stretches of chromatin. Allele-specific higher-order chromatin structure has been observed at multiple imprinted loci, consistent with the observation of allelic binding of the chromatin-organizing factor CTCF at multiple DMRs. However, whether allelic chromatin structure impacts allelic gene expression is not known for most imprinted loci. Here we characterize the mechanisms underlying brain-specific imprinted expression of thePeg13-Kcnk9locus, an imprinted region associated with intellectual disability. We performed region capture Hi-C on mouse brains from reciprocal hybrid crosses and found imprinted higher-order chromatin structure caused by the allelic binding of CTCF to thePeg13DMR. Using an in vitro neuron differentiation system, we showed that imprinted chromatin structure precedes imprinted expression at the locus. Additionally, activation of a distal enhancer induced imprinted expression ofKcnk9in an allelic chromatin structure-dependent manner. This work provides a high-resolution map of imprinted chromatin structure and demonstrates that chromatin state established in early development can promote imprinted expression upon differentiation.

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Section: Discussionmentioning

confidence: 99%

Allelic chromatin structure precedes imprinted expression ofKcnk9during neurogenesis

Loftus,

Bae,

Whilden

et al. 2023

Genes Dev.

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“…Among the network, lncRNA Peg13 regulates the Wnt/β-catenin pathway through the mir-490-3p/psmd11 axis ( 50 ) and attenuates the toxicity of sevoflurane to neural stem cells through the absorption of mir-128-3p while protecting the expression of SOX13 ( 51 ). At the same time, Peg13 can also alleviate hypoxic-ischaemic brain injury in neonatal mice via the mir-20a-5p/XIAP axis ( 52 ). In other studies, knockdown of the m6A-binding protein ythdf2 increased the expression levels of map2k4 and map4k4 mRNA by stabilizing mRNA transcripts.…”

Section: Discussionmentioning

confidence: 99%

Construction of ceRNA and m6A-related lncRNA networks associated with anti-inflammation of AdipoAI

Huang²,

Xie³

et al. 2023

Front. Immunol.

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BackgroundAdiponectin (APN) is an endogenous adipokine secreted from adipocytes that exerts anti-inflammatory properties. AdipoAI is an orally active adiponectin receptor agonist identified by our group that can emulate APN's anti-inflammatory properties through mechanisms that are not fully understood. LncRNAs, a type of noncoding RNA more than 200 bp in length, have been demonstrated to have abundant biological functions, including in anti-inflammatory responses.Materials and ResultIn the current study, we performed a lncRNA microarray in LPS-induced Raw264.7 cells that were prestimulated with AdipoAI and screened 110 DElncRNAs and 190 DEmRNAs. Enrichment analyses were conducted on total mRNAs and DEmRNAs, including GSVA, ssGSEA, GO/KEGG, GSEA, and PPI analysis. Among all these processes, endocytosis was significantly enriched. A coexpression analysis was built based on DElncRNAs and DEmRNAs. Then, using TargetScan and miRwalk to predict related microRNAs of DElncRNAs and DEmRNAs, respectively, we established competing endogenous RNA (ceRNA) networks including 54 mRNAs from 8 GO items. Furthermore, 33 m6A methylation-related marker genes were obtained from a previous study and used for the construction of an m6A-related lncRNA network by coexpression analysis. We identified FTO as the hub gene of the network and 14 lncRNAs that interacted with it. The expression levels of 10 lncRNAs selected from ceRNA and FTO-related lncRNA networks were validated with qRT‒PCR. Finally, macrophage phenotype scores showed that AdipoAI could attenuate the M2b and M2c polarization of macrophages and correlate with the above lncRNAs.ConclusionOur work reveals that lncRNAs might be involved in the anti-inflammation process of AdipoAI in LPS-induced macrophages through the ceRNA network and the epigenetic regulation of m6A. Mechanistically, these lncRNAs associated with AdipoAI might be related to endocytosis and polarization in macrophages and provide new candidates for the anti-inflammatory application of APN and its receptor agonist.

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“…Recently, an increasing number of lncRNAs participating in the onset and progression of sepsis have been identified, such as metastasis-associated lung adenocarcinoma transcript1 (MALAT1) ( Yue et al, 2022 ), cancer susceptibility candidate gene 2 (CASC2) ( Wang R et al, 2022 ), and noncoding RNA activated by DNA damage (NORAD) ( Xie et al, 2022 ).Evidence has demonstrated that the lncRNA paternally expressed 13 (Peg13) plays a protective role against neurological diseases. Peg13 attenuates hypoxic-ischemic brain injury in neonatal murine models by binding to miR-20a-5p to elevate X chromosome-linked inhibitor of apoptosis (XIAP) expression ( Gao et al, 2022 ). Peg13, induced by GLI Family Zinc Finger 2 (Gli2), reduces cerebral ischemia/reperfusion damage via the down-regulation of Yy1 in a PRC2 complex-dependent manner ( Li et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Revealing the role of Peg13: A promising therapeutic target for mitigating inflammation in sepsis

Wang,

Lin,

et al. 2024

Genet. Mol. Biol.

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To investigate the role of Peg13 in modulating the inflammatory response in sepsis, we established Lipopolysaccharide (LPS)-induced 293T cells and mouse models. Peg13 expression was assessed at various time points after infection using RT-qPCR. The levels of high mobility group box 1 (HMGB1) and interleukin-6 (IL-6) were quantified through ELISA. A total of 44 septic patients and 36 healthy participants were recruited to measure Peg13 and HMGB1 levels in the blood. Peg13 demonstrated significant down-regulation in the supernatant of LPS-induced 293T cells and in the blood of LPS-induced mice. Moreover, the levels of proinflammatory cytokines HMGB1 and IL-6 were elevated in both the supernatant of LPS-induced cell models and blood specimens from LPS-induced murine models, and this elevation could be notably reduced by Peg13 suppression. In a clinical context, Peg13 and HMGB1 levels were higher in septic patients compared to healthy subjects. Peg13 exhibited a negative correlation with HMGB1, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) among septic patients. Peg13 mitigates the inflammatory response by reducing the release of proinflammatory cytokines HMGB1 and IL-6 in sepsis, presenting a potential therapeutic target for alleviating inflammation in sepsis treatment.

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Long Non-coding RNA Peg13 Alleviates Hypoxic-Ischemic Brain Damage in Neonatal Mice via miR-20a-5p/XIAP Axis

Cited by 12 publications

References 28 publications

Allelic chromatin structure precedes imprinted expression ofKcnk9during neurogenesis

Allelic chromatin structure precedes imprinted expression ofKcnk9during neurogenesis

Construction of ceRNA and m6A-related lncRNA networks associated with anti-inflammation of AdipoAI

Revealing the role of Peg13: A promising therapeutic target for mitigating inflammation in sepsis

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