Two Triacylglycerol Pathway Genes, Ctdnep1 and Lpin1, Are Down-Regulated by Hsa-Mir-122-5P in Hepatocytes Pubmed



Naderi M¹ ; Pazouki A² ; Arefian E³ ; Hashemi SM⁴ ; Jamshidiadegani F⁵ ; Gholamalamdari O⁵ ; Soudi S⁶ ; Azadmanesh K⁷ ; Samiee SM⁸ ; Merat S¹ ; Fesharaki MG⁹ ; Mondanizadeh M¹⁰ ; Vasei M¹¹ ; Soleimani M¹²
Source: Archives of Iranian Medicine Published:2017

Abstract

Background: Expression of miR-122 is highly specific to hepatocytes of the liver. This miRNA is involved in lipid hemostasisof 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. © 2017, Academy of Medical Sciences of I.R. Iran. All rights reserved.