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Series GSE139830 Query DataSets for GSE139830
Status Public on Nov 02, 2019
Title RNA sequencing analysis of liver after overexpressing of hepatic miR-378
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
Overall design There are two groups, Ad-Ctrl and Ad-378, and three sample per group.
Contributor(s) Sun C, Liu W
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Submission date Nov 01, 2019
Last update date Apr 01, 2020
Contact name chao sun
Phone 15900497204
Organization name Shanghai Institutes for Biological Sciences, University of Chinese Academy ofSciences
Department Shanghai Institutes for Biological Sciences
Lab CAS Key Laboratory of Nutrition, Metabolism and Food Safety
Street address 320 Yueyang Road, Xuhui District, Shanghai, China
City shanghai
State/province shanghai
ZIP/Postal code 200031
Country China
Platforms (1)
GPL21273 HiSeq X Ten (Mus musculus)
Samples (6)
GSM4147102 Ad-ctrl rep1
GSM4147103 Ad-ctrl rep2
GSM4147104 Ad-ctrl rep3
BioProject PRJNA587117
SRA SRP227956

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Supplementary file Size Download File type/resource
GSE139830_RNA-SEQ_Ad_Ctrl_vs_378.xlsx 2.8 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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