Mahmood Naderi1, Abdolreza Pazouki2, Ehsan Arefian3, Seyed Mahmoud Hashemi4, Fatemeh Jamshidi-Adegani5, Omid Gholamalamdari5, Sara Soudi6, Kayhan Azadmanesh7, Siamak Mirab Samiee8, Shahin Merat1, Mohammad Gholami Fesharaki9, Mahdieh Mondanizadeh10, Mohammad Vasei11, Masoud Soleimani12. 1. Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. 2. Minimally Invasive Surgery Research Center, Iran University of Medical Sciences, Tehran, Iran. 3. Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran. 4. Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5. Stem Cell Technology Research Center, Tehran, Iran. 6. Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 7. Department of Virology, Pasteur Institute of Iran, Tehran, Iran. 8. Food and Drug Laboratory Research Center, Tehran, Iran. 9. Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 10. Department of Biotechnology and Molecular Medicine, Arak University of Medical Sciences, Arak, Iran. 11. Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran, Department of Pathology, Tehran University of Medical Sciences, Shariati Hospital, Tehran, Iran. 12. Department of Hematology, Tarbiat Modares University, Tehran, Iran.
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.
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.