Loss of imprinting mutations define both distinct and overlapping roles for misexpression of IGF2 and of H19 lncRNA

Park, Ki-Sun; Mitra, Apratim; Rahat, Beenish; Kim, Kee K.; Pfeifer, Karl

doi:10.1093/nar/gkx896

Cited by 29 publications

(27 citation statements)

References 62 publications

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“…Among several regulators of mTOR signaling that have been exported, we first suggest that the expression of lncRNA H19 is remarkably upregulated by IL-22 in hepatocytes and that the IL-22-STAT3-lncRNA H19 signaling pathway is significant for the activation of mTOR and the preservation of mitochondrial fitness during hepatocyte damage. In agreement with previous studies, we show that lncRNA H19 affects the upstream regulators of mTOR signaling, such as AMPK, AKT proteins, thereby activates mTOR and induces the expression of a subset of metabolic reprogramming regulators in hepatocytes [30,[44][45][46]. Accordingly, we find that lncRNA H19 plays a central role in the inhibition of mitochondrial ROS accumulation and dysfunctional mitochondria elimination in hepatocytes.…”

Section: Discussionsupporting

confidence: 92%

Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury

Chen

Zai

Fan

et al. 2020

Preprint

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AbstractInterleukin 22 (IL-22) is an epithelial survival cytokine that is at present being explored as therapeutic agents for acute and chronic liver injury. However, its molecular basis of protective activities remains poorly understood. Here we demonstrate that IL-22 inhibits the deteriorating metabolic states induced by stimuli in hepatocytes. Specifically, we provide evidence that IL-22 promotes oxidative phosphorylation (OXPHOS) and glycolysis and regulates the metabolic reprogramming related transcriptional responses. IL-22 controls metabolic regulators and enzymes activity through the induction of AMP-activated protein kinase (AMPK), AKT and mammalian target of rapamycin (mTOR), thereby ameliorating mitochondrial. The upstream effector lncRNA H19 also participates in the controlling of these metabolic processes in hepatocytes. Importantly, amelioration of liver injury by IL-22 through activation of metabolism relevant signaling and regulation of mitochondrial function are further demonstrated in cisplatin-induced liver injury and steatohepatitis. Collectively, our results reveal a novel mechanism underscoring the regulation of metabolic profiles of hepatocytes by IL-22 during liver injury, which might provide useful insights from the bench to the clinic in treating and preventing liver diseases.Graphical AbstractOur works demonstrate a critical role of IL-22 in regulating hepatocellular metabolism to treat liver injury via activating STAT3-lncRNA H19-AMPK-AKT-mTOR axis. These findings describe a novel mechanism underscoring the regulation of metabolic states of hepatocytes by IL-22 during liver injury with potentially broad therapeutic insights.

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Section: Discussionsupporting

confidence: 92%

Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury

Chen

Zai

Fan

et al. 2020

Preprint

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“…Therefore, understanding the underlying mechanisms of myogenesis is particularly important. Although thousands of lncRNAs have been identified [38,50], a minority of functional lncRNAs, such as TncRNA [51], lncMD [52], H19 [52][53][54][55][56], and lncIRS1 [57], are involved in mammal myogenesis. MEG3, a differentially expressed lncRNA during postnatal skeletal muscle development in pigs, has four crucial polymorphism sites associated with back fat thickness [39].…”

Section: Discussionmentioning

confidence: 99%

MEG3 Promotes Differentiation of Porcine Satellite Cells by Sponging miR-423-5p to Relieve Inhibiting Effect on SRF

Cheng

Long

Shi

et al. 2020

Cells

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Although thousands of long noncoding RNAs (lncRNAs) have been identified in porcine growth and development, the regulation mechanisms of functional lncRNAs have not been well explored. In this study, using 5′- and 3′-rapid amplification of cDNA ends (RACE) assays, we obtained two different variants of lncRNA maternally expressed gene 3 (MEG3), namely, MEG3 v1 and MEG3 v2, that were both highly expressed in porcine skeletal muscle and in the early stage of the differentiation of porcine satellite cells. Moreover, we identified the core transcript MEG3 v2. Functional analyses showed that MEG3 overexpression could effectively arrest myoblasts in the G1 phase, inhibit DNA replication, and promote myoblast differentiation, whereas MEG3 knockdown resulted in the opposite effects. Interestingly, the expression of serum response factor (SRF), a crucial transcription factor for myogenesis process, remarkably increased and decreased in mRNA and protein levels with the respective overexpression and knockdown of MEG3. Dual luciferase reporter assay showed that MEG3 could attenuate the decrease of luciferase activity of SRF induced by miR-423-5p in a dose-dependent manner. MEG3 overexpression could relieve the inhibitory effect on SRF and myoblast differentiation induced by miR-423-5p. In addition, results of RNA immunoprecipitation analysis suggested that MEG3 could act as a ceRNA for miR-423-5p. Our findings initially established a novel connection among MEG3, miR-423-5p, and SRF in porcine satellite cell differentiation. This novel role of MEG3 may shed new light on understanding of molecular regulation of lncRNA in porcine myogenesis.

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“…Previous research has shown that the H19/ IGF2 locus, both genes share a common set of enhancers, which are located downstream of the H19 gene [18]. Differentially methylated regions in these two genes have also been implicated in a range of biological processes and diseases, largely because of their role regulating composition of the body [39][40][41][42]; however, little research has been carried out in terms of PCOS in this respect. One previous study showed that IGF2 is a host gene of miR-483-5p and recorded significantly lower levels of IGF2 in the cumulus cells of women with PCOS [43].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA H19 is associated with polycystic ovary syndrome in Chinese women: a preliminary study

et al. 2019

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Polycystic ovary syndrome (PCOS) represents a serious reproductive and endocrine condition and is associated with high incidence rates. H19 is a compelling long noncoding RNA (lncRNA) which carries out a range of biological functions. However, prior to this study, little was known as to whether there was an association between lncRNA H19 and PCOS. In the current study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to determine lncRNA H19 expression levels in peripheral blood leukocytes from patients with PCOS and compared this data with that derived from normal controls. We also screened data for potential relationships between lncRNA H19 and a range of endocrine variables in PCOS. The expression of lncRNA H19 was significantly higher in cases of PCOS than in controls. Individuals exhibiting higher expression levels of lncRNA H19 were associated with a significantly higher risk of PCOS than those with lower expression levels. Moreover, lncRNA H19 expression was positively correlated with fasting plasma glucose levels; this was the case with both raw data, and after adjustment for age and BMI in the PCOS group. However, lncRNA H19 expression showed no significant correlation with total testosterone or insulin resistance in either PCOS cases or the controls. In conclusion, we demonstrate the first evidence to indicate that lncRNA H19 is associated with PCOS, suggesting that elevated lncRNA H19 levels are a risk factor for PCOS. For susceptible individuals, lncRNA H19 may represent a useful biomarker of the early stages of endocrine and metabolic disorders in PCOS.

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Loss of imprinting mutations define both distinct and overlapping roles for misexpression of IGF2 and of H19 lncRNA

Cited by 29 publications

References 62 publications

Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury

Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury

MEG3 Promotes Differentiation of Porcine Satellite Cells by Sponging miR-423-5p to Relieve Inhibiting Effect on SRF

Long non-coding RNA H19 is associated with polycystic ovary syndrome in Chinese women: a preliminary study

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