The H19 lincRNA is a developmental reservoir of miR-675 which suppresses growth and Igf1r
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ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR062252.fastq.gz | Fastqsanger.gz | |||
| ERR062253.fastq.gz | Fastqsanger.gz |
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Project description:Investigate the effect of an H19 knockout on gene expression
2012-05-04 | E-MTAB-895 | biostudies-arrayexpress
Project description:The H19 large intergenic non-coding RNA (lincRNA) is one of the most highly abundant and conserved transcripts in mammalian development, being expressed in both embryonic and extra-embryonic cell lineages, yet its physiological function is unknown. Here we show that miR-675, a microRNA (miRNA) embedded in H19's first exon, is expressed exclusively in the placenta from the gestational time point when placental growth normally ceases, and placentas that lack H19 continue to grow. Overexpression of miR-675 in a range of embryonic and extra-embryonic cell lines results in their reduced proliferation; targets of the miRNA are upregulated in the H19 null placenta, including the growth-promoting insulin-like growth factor 1 receptor (Igf1r) gene. Moreover, the excision of miR-675 from H19 is dynamically regulated by the stress-response RNA-binding protein HuR. These results suggest that H19's main physiological role is in limiting growth of the placenta before birth, by regulated processing of miR-675. The controlled release of miR-675 from H19 may also allow rapid inhibition of cell proliferation in response to cellular stress or oncogenic signals.
| S-EPMC3389517 | biostudies-literature
Project description:Regulation of brown fat homeostasis by H19 lincRNA
| PRJNA477815 | ENA
Project description:Changes in microRNA expression in Igf2-p and H19-m mouse embryos (E9.5) were determined in order to assess whether perturbation of miR-483* and miR-675 in Igf2-p and H19-m mutants was likely to have contributed to a modification of tumour phenotype. The Igf2 gene contains miR-483* but the targeted deletion of Igf2-p in these mice spares the region encoding this microRNA. The H19 gene contains miR-675 and its expression was mono-allelelic in heterozygous H19-m mice as evidenced by a significant reduction in miR-675 in these mice relative to WT.
2011-12-01 | E-MTAB-873 | biostudies-arrayexpress
Project description:Regulation of brown fat homeostasis by H19 lincRNA [I]
| PRJNA477820 | ENA
Project description:Regulation of brown fat homeostasis by H19 lincRNA [II]
| PRJNA477821 | ENA
Project description:Igf2 and H19 are linked, reciprocally imprinted genes that play critical roles in mammalian development. Igf2 encodes a peptide hormone, Insulin-like Growth Factor 2, that binds to the InsR and Igf1R receptor kinases to regulate cell growth and metabolism through well-established pathways. H19 encodes a 2.3 kb lncRNA whose biochemical actions are only now being identified. Here we use a mouse model to investigate cardiomyopathies associated with maternal loss of imprinting at the locus. Increased circulating levels of IGF2 during fetal development result in activation of pAKT/mTOR signaling in cardiomyocytes to cause cellular hypertrophy and hyperplasia in neonatal hearts. This neonatal hypertrophy is unaffected by H19 RNA levels. However, loss of H19 does cause fibrosis and progressive cardiac pathology in adult mice. In hearts, H19 expression is concentrated in endothelial cells associated with blood vessels and capillaries and loss of H19 results in high incidence of trans differentiation of these cells to smooth muscle. H19 encoded miRNAs 675-3p and -5p are not sufficient to promote normal development. Thus these experiments define a novel role for the H19 lncRNA in regulating cell fate.
2020-03-01 | GSE111418 | GEO
Project description:Increases in organismal energy expenditure, as during cold exposure or exercise training, can improve metabolic health. This process is dependent also on brown adipose tissue (BAT) thermogenesis in mice and humans. Understanding and harnessing the molecular circuits activating BAT function is thus of great interest to devise novel approaches to counteract obesity and type 2 diabetes (T2D). In contrast to protein-coding genes, the role of long noncoding RNAs (lncRNAs) during BAT differentiation and function remains poorly understood. To address this, we performed RNA-Seq and identified the maternal allele-specific (imprinted) lncRNA H19 increased upon cold-mediated BAT activation and decreased upon chronic diet-induced obesity (DIO) BAT dysfunction. An inverse correlation of H19 expression with body-mass indices (BMI) was observed in a cohort of >160 lean and obese humans. H19 silencing impaired adipogenesis and oxidative metabolism in brown but not white adipocytes, while H19 gain-of-function increased nutrient oxidation and mitochondrial respiration, thus supporting a BAT-regulatory role for H19. In vivo H19 overexpression protected against DIO, improved insulin sensitivity and rescued DIO-mediated defects in energy expenditure in conjunction with improved mitochondrial biogenesis. In contrast, BAT-selective H19 loss decreased energy dissipation and sensitized towards high fat diet-induced body weight gains. When investigating other parent-of-origin specific, monoallelically expressed genes, we strikingly observed that paternally expressed genes (PEGs) were largely absent from BAT and coordinately downregulated during brown adipogenesis, whilst the same gene set was robustly expressed in white fat stores, a phenomenon not observed for maternally expressed genes (MEGs). Using H19 loss- and gain-of-function in primary adipocytes, we demonstrate that H19 acts as ‘PEG gatekeeper’ in brown, not white adipocytes, potentially due to recruitment of PEG-inactivating H19-MBD1 complexes in mature brown adipocytes. The exclusive PEG expression in white adipose tissuer could underly the observed susceptibility of mice exhibiting high PEG abundances towards DIO-evoked weight gain. Collectively, we here define novel roles for the imprinted lncRNA H19 in brown adipocyte differentiation and function in vitro, control of energy expenditure in vivo and repression of paternal allele-specific gene expression in BAT. This has far-reaching implications for our understanding of how monoallelical gene expression affects metabolic eustasis in both rodent models and, potentially, human patients.
2018-06-26 | GSE116226 | GEO
Project description:Increases in organismal energy expenditure, as during cold exposure or exercise training, can improve metabolic health. This process is dependent also on brown adipose tissue (BAT) thermogenesis in mice and humans. Understanding and harnessing the molecular circuits activating BAT function is thus of great interest to devise novel approaches to counteract obesity and type 2 diabetes (T2D). In contrast to protein-coding genes, the role of long noncoding RNAs (lncRNAs) during BAT differentiation and function remains poorly understood. To address this, we performed RNA-Seq and identified the maternal allele-specific (imprinted) lncRNA H19 increased upon cold-mediated BAT activation and decreased upon chronic diet-induced obesity (DIO) BAT dysfunction. An inverse correlation of H19 expression with body-mass indices (BMI) was observed in a cohort of >160 lean and obese humans. H19 silencing impaired adipogenesis and oxidative metabolism in brown but not white adipocytes, while H19 gain-of-function increased nutrient oxidation and mitochondrial respiration, thus supporting a BAT-regulatory role for H19. In vivo H19 overexpression protected against DIO, improved insulin sensitivity and rescued DIO-mediated defects in energy expenditure in conjunction with improved mitochondrial biogenesis. In contrast, BAT-selective H19 loss decreased energy dissipation and sensitized towards high fat diet-induced body weight gains. When investigating other parent-of-origin specific, monoallelically expressed genes, we strikingly observed that paternally expressed genes (PEGs) were largely absent from BAT and coordinately downregulated during brown adipogenesis, whilst the same gene set was robustly expressed in white fat stores, a phenomenon not observed for maternally expressed genes (MEGs). Using H19 loss- and gain-of-function in primary adipocytes, we demonstrate that H19 acts as ‘PEG gatekeeper’ in brown, not white adipocytes, potentially due to recruitment of PEG-inactivating H19-MBD1 complexes in mature brown adipocytes. The exclusive PEG expression in white adipose tissuer could underly the observed susceptibility of mice exhibiting high PEG abundances towards DIO-evoked weight gain. Collectively, we here define novel roles for the imprinted lncRNA H19 in brown adipocyte differentiation and function in vitro, control of energy expenditure in vivo and repression of paternal allele-specific gene expression in BAT. This has far-reaching implications for our understanding of how monoallelical gene expression affects metabolic eustasis in both rodent models and, potentially, human patients.
2018-06-26 | GSE116225 | GEO
Project description:Galangin, a natural flavonoid, derived from honey and Alpinia officinarum Hance (Zingiberaceae) has excellent was anti-tumor and anti-inflammatory properties. w It has been extensively studied as a novel therapeutic agent forhich was widely used in the treatment of various cancers. However, the effect of galangin in HCC remains elusive. Using RNA sequencing, the differential expression of LncRNA in MHCC97H cells treated with galangin was investigated in the present study. Furthermore, the expression of H19 was also determined in MHCC97H cells following treatment with galangin. And the effect of knockdown and overexpression of H19 on cell apoptosis, cell cycle, migration and invasion of HCC cells was also evaluated. Moreover, the in vivo effect of galangin on tumor development was also determined in nude mice. This study identified aT total of 50 LncRNAs were to be significantly differentially expressed by RNA-seq analysis in MHCC97H cells treated with galangin. It has been demostreated that noncoding RNA H19 are abnormally expressed in different cancers. Our results showed that Besides, the expression of H19 was markedly reduced after following treatment with galangin treatment in MHCC97H cells. In addition, galangin could increase the occurrence of cell apoptosis. Moreover, compared to the Control group, the galangin-treated group inhibited cell migration and invasion in MHCC97H cells.To further investigated if H19 expression pattern affect cell apoptosis, migration and invasion, knock down and overexpression of H19 vector were constructed. The results of the knockdown of H19 expression showed knock down of H19 expression increased cell apoptosis and decreasedinhibited invasion. In addition, RNA-seq data showed also identified 161 mRNA which were was significantly differentially expressed after following treatment withof galangin. To further determine the underlying mechanism,confirmed cell apoptosis, p53 protein and its related proteins were was analyzed through micor RNA 675-3p (miR675-3p) which was in the H19 locus. Notably, Tthe results indicatedshowed that reduced knockdown of H19 and miR675 induced the protein expression of p53, eventually promoting cell apoptosis expression of H19 and miR675-3p increased p53 expression in MHCC97H cells. These results indicated that galangin promoted cell apoptosis through the regulation of H19 and miR675 expression in MHCC97H cells. Furthermorely, galangin was used to treated in nude mice. Tthe in vivo result showed that compared to the Control group, inhibited tumor growth was remarkably suppressed and reduced expression of H19 in galangin-treated group. Taken together, these results indicated that galangin regulated cell apoptosis which associate with p53 protein through H19 and miR675 expression in MHCC97H cells.Collectively, our data suggested that galangin plays a role in hepatocarcinogenesis through regulation of H19 expression pattern.
2020-08-12 | GSE142680 | GEO