Mutation of miR-21 targets endogenous lipoprotein receptor-related protein 6 and nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Although miR-21 has been implicated in nonalcoholic fatty liver disease, it is unknown whether miR-21 could function as a therapeutic target. Here, we perform transfection analysis of miR-21 mimic or control mimic to evaluate the effects of miR-21 expression levels on human HepG2 nonalcoholic fatty liver cells. We used siRNA techniques to knock down miR-21 in HepG2 and control 293T cell lines, and then monitored lipid production and the expression levels of genes involved in lipid metabolism. The effects of miR-21 expression levels on LDL receptor-related protein 6 (LRP6) expression were evaluated using qRT-PCR and western blot analyses. Luciferase reporter assays were conducted to confirm the effects of miR-21 expression levels on LRP6. The results indicated that transfection of miR-21 mimic induced changes in the expression levels of lipogenic enzymes, including acetyl-CoA carboxylase 1 (ACC1), stearoyl CoA desaturase (1SCD1), sterol regulatory element-binding protein 1 (SREBP1), and liver X receptor alpha (LXRα). Transfection of miR-21 mimic suppressed the transcription and translation of LRP6 at the mRNA and protein levels, whereas miR-21 knockdown increased the expression levels of LRP6. Transfection of miR-21 mimic in HepG2 cells also induced lipid production and triggered the expression of critical lipid metabolic enzymes. These data suggest that mutation of miR-21 may be a new therapeutic strategy to treat nonalcoholic fatty liver diseases by targeting endogenous LRP6.
Department of Gastroenterology, Affiliated Hospital of Luzhou Medical College Luzhou 646000, China.
Chang-Ping
CP
Li
School of Medicine, Shanghai Jiao Tong University Shanghai 200025, China.
Hong-Jue
HJ
Li
Department of Gastroenterology, Affiliated Hospital of Luzhou Medical College Luzhou 646000, China.
Jiao
J
Nie
Department of Gastroenterology, Affiliated Hospital of Luzhou Medical College Luzhou 646000, China.
Xia
X
Chen
Department of Gastroenterology, Affiliated Hospital of Luzhou Medical College Luzhou 646000, China.
Xian
X
Zhou
LDL receptor-related protein 6 (LRP6); Nonalcoholic fatty liver disease; low-density lipoprotein (LDL); miR-21