Naderi Mahmood, Pazouki Abdolreza, Arefian Ehsan, Hashemi Seyed Mahmoud, Jamshidi-Adegani Fatemeh, Gholamalamdari Omid, Soudi Sara, Azadmanesh Kayhan, Mirab Samiee Siamak, Merat Shahin, Gholami Fesharaki Mohammad, Mondanizadeh Mahdieh, Vasei Mohammad, Soleimani Masoud
Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Minimally Invasive Surgery Research Center, Iran University of Medical Sciences, Tehran, Iran.
Arch Iran Med. 2017 Mar;20(3):165-171.
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.
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.
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.
Our findings suggest that up-regulation of miR-122 can trigger the compensatory response of LPIN1 and CTDNEP1 in hepatosteatosis.
miR-122的表达对肝脏的肝细胞具有高度特异性。这种微小RNA参与组织的脂质稳态；然而，对其在脂质稳态中的功能尚无全面了解。
由于肝细胞负责体内部分三酰甘油（TAG）的合成，我们推测，作为该组织中最丰富的微小RNA，miR-122可能通过靶向参与其产生途径的关键酶来调节TAG代谢。对miR-122假定靶标的系统计算分析确定了TAG途径中的CTDNEP1和LPIN1基因。我们使用双荧光素酶报告基因检测、定量RT-PCR以及蛋白质印迹法来证实miR-122对TAG途径中CTDNEP1和LPIN1的抑制作用。
对肝脂肪变性患者肝穿刺活检组织进行实时PCR检测显示，肝脂肪变性时miR-122表达上调。令人惊讶的是，在临床样本中，miR-122已确定靶标的蛋白质和RNA水平也上调，这可能是对高水平miR-122的不成比例的反馈反应。
我们的研究结果表明，miR-122上调可触发肝脂肪变性中LPIN1和CTDNEP1的代偿反应。
