Overexpression of circ PTK2 suppresses the progression of nonalcoholic fatty liver disease via the miR‐200c/SIK2/PI3K/Akt axis.

Excessive hepatic lipid accumulation is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A previous study showed that the circular RNA (circRNA) PTK2 was significantly downregulated in NAFLD mice. However, the detailed function of circ PTK2 in NAFLD remains unclear. A high‐fat diet (HFD) was used to establish a mouse model of NAFLD, and free fatty acid (FFA) treatment was used to establish an in vitro model of NAFLD. Oil red O staining was used to evaluate lipid accumulation. The pathological changes in mice were observed by HE staining. Western blotting and RT–qPCR were applied to assess protein and mRNA levels, respectively. A dual luciferase reporter assay and RIP were used to explore the relationship among circ PTK2, miR‐200c and SIK2. Circ PTK2 and SIK2 were downregulated and miR‐200c was upregulated in NAFLD. Upregulation of circ PTK2 reversed lipid accumulation in FFA‐treated HepG2 cells. Moreover, circ PTK2 bound to miR‐200c, and SIK2 was identified as the direct target of miR‐200c. Moreover, the miR‐200c inhibitor‐induced decrease in lipid accumulation was reversed by SIK2 knockdown. Furthermore, the impact of circ PTK2 overexpression on PI3K/Akt signaling was partially reversed by SIK2 silencing. Circ PTK2 overexpression alleviates NAFLD development via the miR‐200c/SIK2/PI3K/Akt axis. Thus, our work might provide new methods for NAFLD treatment. [ABSTRACT FROM AUTHOR]