Long non­coding RNA HR1 participates in the expression of SREBP­1c through phosphorylation of the PDK1/AKT/FoxO1 pathway.

Sterol regulatory element binding protein­1c (SREBP­1c), which serves an essential role in the process of fat synthesis, is a key adjustment factor that regulates the dynamic balance of lipid metabolism. SREBP­1c activates the transcription of multiple genes encoding for enzymes involved in the synthesis of triglycerides (TG) and fatty acids (FA) and accelerates lipid synthesis. Previous analysis indicated that long non­coding RNA HCV regulated 1 (lncHR1) participates in lipid metabolism in vivo and regulates the level of SREBP­1c protein. However, the mechanism of lncHR1 in regulating SREBP­1c levels has not been revealed. In the present study, a fatty degeneration cell model was used to study how lncHR1 regulates the SREBP­1c protein at the cellular level. Furthermore TG accumulation was assessed according to morphological analysis. Reverse transcription­quantitative polymerase chain reaction and western blotting were used to detected the expression of SREBP­1c. An activator and an inhibitor of phosphoinositide 3­kinase/AKT phosphorylation (IGF­1 and LY294002, respectively) were used to study the effect of lncHR1 on this pathway. It was verified that lncHR1 regulated SREBP­1c levels and the phosphorylation of AKT in the steatosis cell model. Detailed molecular mechanisms mediated by lncHR1 were associated with the phosphorylation AKT/FoxO1 in Huh7 cell lines. Simultaneously, lncHR1 affected the location of FoxO1 inside and outside of the nucleus. Furthermore, the phosphorylation of PDK1 upstream of AKT was regulated through overexpression or knockdown lncHR1, as determined by western blotting. Taken together, these data show that lncHR1 inhibits SREBP­1c levels through the phosphorylation of the PDK1/AKT/FoxO1 axis.