MiR-451a attenuates free fatty acids-mediated hepatocyte steatosis by targeting the thyroid hormone responsive spot 14 gene
| Autor: | Fei Wang, Nan Li, Rong Huang, Ni Zeng, Qing Wang, Wen Chen, Hongmei Jiang, Ruobi Li, Min Xia |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Fatty Acids Nonesterified Diet High-Fat Biochemistry 03 medical and health sciences 0302 clinical medicine Endocrinology Nonalcoholic fatty liver disease microRNA medicine Animals Humans THRSP Gene Molecular Biology 3' Untranslated Regions Chemistry Three prime untranslated region Lipogenesis Nuclear Proteins Hep G2 Cells medicine.disease Cell biology Mice Inbred C57BL MicroRNAs 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Hepatocyte Hepatic stellate cell Hepatocytes Steatosis Fatty Acid Synthases Stearoyl-CoA Desaturase Octamer Transcription Factor-1 Transcription Factors |
| Zdroj: | Molecular and cellular endocrinology. 474 |
| ISSN: | 1872-8057 |
| Popis: | The thyroid hormone responsive spot 14 (THRSP) gene is a de novo lipogenesis-related gene that plays a significant role in the initiation and development of nonalcoholic fatty liver disease (NAFLD). Several previous studies had shown that endogenous and environmental factors could regulate the expression of THRSP. The role of microRNAs (miRNAs), however, in controlling THRSP expression has not been investigated. In this study, we first constructed the hepatic steatosis cell model by using a mixture of free fatty acids (FFAs; oleate/palmitate, 2:1 ratio) to treat and demonstrate the promotive role of THRSP in lipid accumulation in hepatic cells. By analyzing the photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) database and performing a luciferase reporter assay, we confirmed that microRNA-451a specifically binds to mouse and human THRSP 3'UTR and inhibits its activity. Overexpression of miR-451a efficiently reduced THRSP mRNA and protein expression as well as triglyceride (TG) accumulation in cultured hepatic cells (AML12 and HepG2). Moreover, overexpression of miR-451a significantly decreases TG accumulation in the livers of mice injected with an miR-451a agomir. All these results demonstrated that miR-451a might participate in the FFA-induced hepatic steatosis by regulating the expression of the THRSP gene which represents a new potential target for NAFLD therapy. |
| Databáze: | OpenAIRE |
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