MiR-205 modulates abnormal lipid metabolism of hepatoma cells via targeting acyl-CoA synthetase long-chain family member 1 (ACSL1) mRNA.
The abnormal lipid metabolism is considered as a hallmarker of tumorigenesis. Liver is the central organ for metabolic homeostasis. Hence, the development of hepatocellular carcinoma (HCC) always exhibits alterations of metabolism. MicroRNAs emerge as key post-transcriptional modulators of gene expression in physiologic and pathologic states. Here, we aim to explore the mechanism of abnormal lipid metabolism of hepatoma cells. Previously, our group reported that miR-205 as a tumor suppressor was down-regulated in HCC. Therefore, we supposed that miR-205 might be involved in the event. Interestingly, in this study we uncover that miR-205 deregulates lipid metabolism in HCC through targeting acyl-CoA synthetase long-chain family member 1 (ACSL1) mRNA, which is an important and abundant lipid metabolism enzyme in liver. We identified that miR-205 was able to down-regulate ACSL1 via targeting its 3'UTR in the cells. Oil red O staining showed that miR-205 disordered the lipogenesis in hepatoma cells and anti-miR-205 resulted in the accumulation of triglyceride in the cells depending on ACSL1. Moreover, we validated that the low levels of miR-205 were negatively related to high levels of ACSL1 in clinical HCC tissues. The expression levels of ACSL1 and its metabolite triglyceride levels were remarkably increased in hepatitis B virus X protein (HBx)-induced liver cancer tissues from the HBx transgenic mice model. Thus, we conclude that miR-205-targeted ACSL1 may contribute to the abnormal lipid metabolism of liver cancer. Our finding provides new insights into the dysregulation of lipid metabolism in HCC mediated by miR-205 targeting ACSL1 mRNA.
Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
Ming
M
Cui
Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
Yue
Y
Wang
Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
Baodi
B
Sun
Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
Zelin
Z
Xiao
Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
Lihong
L
Ye
Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China. Electronic address: zhangxd@nankai.edu.cn.
Xiaodong
X
Zhang
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003066:Coenzyme A Ligases / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins
D020413:3' Untranslated Regions; D003066:Coenzyme A Ligases; D035683:MicroRNAs; D012333:RNA, Messenger; D015534:Trans-Activators; D014280:Triglycerides; D054334:Viral Regulatory and Accessory Proteins; C534425:MIR205, human; C057628:hepatitis B virus X protein; C544400:ACSL1 protein, mouse; C583414:ACSL1 protein, human
ACSL1; Abnormal lipid metabolism; Hepatocellular carcinoma; miR-205