Title of article :
Two Triacylglycerol Pathway Genes, CTDNEP1 and LPIN1, are Down-Regulated by hsa-miR-122-5p in Hepatocytes
Author/Authors :
Naderi, Mahmood Digestive Disease Research Institute - Tehran University of Medical Sciences , Pazouki, Abdolreza Minimally Invasive Surgery Research Center - Iran University of Medical Sciences , Arefian, Ehsan Department of Microbiology - School of Biology - College of Science, University of Tehran , Hashemi, Mahmoud Department of Immunology - Shahid Beheshti University of Medical Sciences , Jamshidi Adegani, Fatemeh Stem Cell Technology Research Center - Tehran , Gholamalamdari, Omid Department of Immunology - Tarbiat Modares University , Soudi, Sara Department of Virology - Pasteur Institute of Iran , Azadmanesh, Kayhan Food and Drug Laboratory Research Center - Tehran , Mirab Samiee, Siamak Digestive Disease Research Institute - Tehran University of Medical Sciences , Merat, Shahin Department of Biostatistics - Faculty of Medical Sciences - Tarbiat Modares University , Gholami Fesharaki, Mohammad Department of Biotechnology and Molecular Medicine - Arak University of Medical Sciences , Mondanizadeh, Mahdieh Digestive Disease Research Institute - Tehran University of Medical Sciences , Vasei, Mohammad Department of Hematology - Tarbiat Modares University
Abstract :
Background
Expression of miR-122 is highly specific to hepatocytes of the liver. This miRNA is involved in lipid hemostasis of the tissue; however, there is no comprehensive understanding of its function in lipid hemostasis.
Materials and Methods
Since hepatocytes are responsible for part of Triacylglycerol (TAG) synthesis in the body, we hypothesized that miR-122, as the most abundant miRNA in the tissue, might regulate TAG metabolism by targeting key enzymes that are involved in its production pathway. A systematic computational analysis of putative targets of miR-122 identified CTDNEP1 and LPIN1 genes in the TAG pathway. We used dual-luciferase reporter assay, quantitative RT-PCR as well as western blot to confirm the repressive effect of miR-122 on CTDNEP1 and LPIN1 in TAG pathway.
Results
Real time PCR on liver needle biopsies with hepatosteatosis showed that miR-122 is up-regulated in hepatosteatosis. Surprisingly, the protein and RNA level of identified targets of miR-122 are also up-regulated in clinical samples, probably as a disproportionate feedback response to the high level of miR-122.
Conclusion
Our findings suggest that up-regulation of miR-122 can trigger the compensatory response of LPIN1 and CTDNEP1 in hepatosteatosis.
Keywords:
Keywords :
Lipid metabolism , miR , 122 , NAFLD , triglycerides
