RNA sequencing analysis of liver after overexpressing of hepatic miR-378
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ABSTRACT:
PROVIDER: PRJNA587117 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10385386_1.fastq.gz | Fastqsanger.gz | |||
| SRR10385386_2.fastq.gz | Fastqsanger.gz | |||
| SRR10385387_1.fastq.gz | Fastqsanger.gz | |||
| SRR10385387_2.fastq.gz | Fastqsanger.gz | |||
| SRR10385388_1.fastq.gz | Fastqsanger.gz |
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Project description:An improved mechanistic understanding of the thyroid hormone (TH) action on bile acid (BA) synthetic pathway, the major route for cholesterol elimination, will facilitate the identification of novel therapeutic targets for hypercholesterolemia. Here, we show that hepatic miR-378 is positively regulated by TH. Transient overexpression of miR-378 in the liver of mice reduces the serum cholesterol levels, which is accompanied with an upregulation of key enzymes involved in the intrahepatic conversion of cholesterol to BAs. Importantly, transgenic mice with liver-specific and moderate overexpression of miR-378 also display a decrease in serum cholesterol levels accompanied with an enhanced BA synthesis and are resistant to diet-induced hypercholesterolemia. In contrast, mice lacking miR-378 exhibit an elevation of serum cholesterol levels accompanied with an impaired BA synthesis. Mechanistic studies reveal that hepatic miR-378 regulates BA synthesis and cholesterol homeostasis through its direct target gene MAFG, which is a transcriptional repressor of BA synthetic genes. We also show that miR-378 serves as an essential component in either incoherent or coherent feed-forward loop to confer robust and precise controls on BA synthesis in response to TH signalling. Together, we identify a previously undescribed miR-378-mediated mechanism underlying the cholesterol-lowering effect of TH. Our findings not only add a new dimension to our understanding the regulation of BA synthesis by TH, but also provide new therapeutic regimens to manage serum cholesterol levels.
2019-11-02 | GSE139830 | GEO
Project description:An improved mechanistic understanding of the thyroid hormone (TH) action on bile acid (BA) synthetic pathway, the major route for cholesterol elimination, will facilitate the identification of novel therapeutic targets for hypercholesterolemia. Here, we show that hepatic miR-378 is positively regulated by TH. Transient overexpression of miR-378 in the liver of mice reduces the serum cholesterol levels, which is accompanied with an upregulation of key enzymes involved in the intrahepatic conversion of cholesterol to BAs. Importantly, transgenic mice with liver-specific and moderate overexpression of miR-378 also display a decrease in serum cholesterol levels accompanied with an enhanced BA synthesis and are resistant to diet-induced hypercholesterolemia. In contrast, mice lacking miR-378 exhibit an elevation of serum cholesterol levels accompanied with an impaired BA synthesis. Mechanistic studies reveal that hepatic miR-378 regulates BA synthesis and cholesterol homeostasis through its direct target gene MAFG, which is a transcriptional repressor of BA synthetic genes. We also show that miR-378 serves as an essential component in either incoherent or coherent feed-forward loop to confer robust and precise controls on BA synthesis in response to TH signalling. Together, we identify a previously undescribed miR-378-mediated mechanism underlying the cholesterol-lowering effect of TH. Our findings not only add a new dimension to our understanding the regulation of BA synthesis by TH, but also provide new therapeutic regimens to manage serum cholesterol levels
2019-10-29 | GSE139491 | GEO
Project description:Dysregulated Genes between miR-378 vs. negative control ovarian cancer cells We transfected ovarian cancer cell lines with miR-378 or negative control
2013-04-30 | E-GEOD-46454 | biostudies-arrayexpress
Project description:Dysregulated Genes between miR-378 vs. negative control ovarian cancer cells
2013-04-30 | GSE46454 | GEO
Project description:To explore the circadian functions of the miRNAs derived from these circadian primary miRNA transcripts, we focused on miR-378 and examined the transcriptome changes in mouse livers upon miR-378 over-expression at two circadian time points, CT10 and CT22. First, we observed a significant over-representation of the circadian oscillating genes affected by miR-378 over-expression. Cell cycle genes are further enriched in the affected circadian oscillating genes, which implied that miR-378 mediates the circadian control of cell cycle. Our examination of circadian regulatory network involving miR-378 suggests that miR-378 mediates the circadian control of cell cycle and metabolism by forming either coherent or incoherent feed-forward loops with circadian TFs.
2016-09-21 | GSE73308 | GEO
Project description:Rationale: MicroRNAs play key roles in hypertrophic stress responses. miR-378(-3p) is a highly abundant, cardiomyocyte-enriched microRNA whose downregulation in pressure-overload has been suggested as detrimental to the heart. Previous studies have utilized systemic anti-miR or microRNA-encoding virus administration, and thus questions regarding the cardiomyocyte-autonomous roles of miR-378 remain. Objective: To examine whether persistent overexpression of miR-378 in cardiomyocytes alters the phenotype of the unstressed heart, whether its overexpression is beneficial or deleterious in the setting of pressure-overload, and to comprehensively identify its cardiomyocyte-specific effects on mRNA regulation. Methods and Results: Cardiac function was compared in young (10-12 week-old) mice overexpressing miR-378 in the heart under the control of the Myh6 promoter (alphaMHC-miR-378 mice), in older (40 week-old) mice and their age-matched wild-type controls. Older alphaMHC-miR-378 mice exhibited decreased fractional shortening and modest chamber dilation with an increase in cardiomyocyte length. When subjected to pressure-overload, cardiomyocyte length was increased in young alphaMHC-miR-378 mice, but fractional shortening declined precipitously over two weeks. Transcriptome profiling of wild-type and alphaMHC-miR-378 hearts in unstressed and pressure-overload conditions revealed dysregulation of several upstream metabolic and mitochondrial genes in alphaMHC-miR-378 hearts, compromising the reprogramming that occurs during early adaptation to pressure overload. Ago2 immunoprecipitation with mRNA sequencing revealed novel miR-378 cardiac mRNA targets including Akt1 and Epac2 and demonstrated the contextual nature of previously described miR-378 targeting events. Conclusions: Long-term upregulation of miR-378 levels in the heart is not innocuous and exacerbates contractile dysfunction in pressure-overload hypertrophy through numerous signaling mechanisms.
2015-09-30 | GSE61734 | GEO
Project description:miR-33 is an intronic microRNA within the gene encoding the SREBP2 transcription factor. Like its host gene, miR-33 has been shown to be an important regulator of lipid metabolism. Inhibition of miR-33 has been shown to promote cholesterol efflux in macrophages by targeting the cholesterol transporter ABCA1, thus reducing atherosclerotic plaque burden. Inhibition of miR-33 has also been shown to improve high-density lipoprotein (HDL) biogenesis in the liver and increase circulating HDL-C levels in both rodents and nonhuman primates. However, evaluating the extent to which these changes in HDL metabolism contribute to atherogenesis has been hindered by the obesity and metabolic dysfunction observed in whole-body miR-33–knockout mice. To determine the impact of hepatic miR-33 deficiency on obesity, metabolic function, and atherosclerosis, we have generated a conditional knockout mouse model that lacks miR-33 only in the liver. Characterization of this model demonstrates that loss of miR-33 in the liver does not lead to increased body weight or adiposity. Hepatic miR-33 deficiency actually improves regulation of glucose homeostasis and impedes the development of fibrosis and inflammation. We further demonstrate that hepatic miR-33 deficiency increases circulating HDL-C levels and reverse cholesterol transport capacity in mice fed a chow diet, but these changes are not sufficient to reduce atherosclerotic plaque size under hyperlipidemic conditions. By elucidating the role of miR-33 in the liver and the impact of hepatic miR-33 deficiency on obesity and atherosclerosis, this work will help inform ongoing efforts to develop novel targeted therapies against cardiometabolic diseases.
2021-02-11 | PXD023471 | Pride
Project description:The files represent mRNAseq data of the HL60 cell line (untransduced), and duplicate samples of HL60s transduced with empty (scrambled) control vector (System Biosciences, Cat. #MZIP000-VA-1) and duplicate samples of HL60s transduced with miRZip anti-miRNA Expression lentivector for miR-378-3p (System Biosciences, Cat# CS970A-1).
2022-05-20 | GSE175434 | GEO
Project description:Thyroid hormone-responsive miR-378 modulates cholesterol homeostasis by regulating hepatic bile acid synthesis
| PRJNA579974 | ENA
Project description:miR-378-3p Knockdown Mimics of MDS
| PRJNA732395 | ENA