Myocyte enhancer factor 2D promotes hepatocellular carcinoma through AMOTL2/YAP signaling that inhibited by luteolin.

Hepatocellular carcinoma (HCC) is one of the deadliest malignancies in the world. There is a lack of effective treatment. Previous studies have shown that myocyte enhancer factor 2D (MEF2D) promotes the progression of HCC. Underlying mechanisms have not been fully elucidated. In this study, we reported experimental results obtained using double luciferase. Our results showed that AMOTL2, a negative regulator of Hippo/YAP signaling, and the MEF2 cis-acting element in the upstream region of its promoter bind to MEF2D, inhibiting its transcriptional expression. Studies confirmed that MEF2D affected the protein expression level of AMOTL2 and the YAP signaling activation. It promoted the migration and proliferation of hepatoma cells. We found that luteolin, a natural flavonoid, has anti-tumor activity in HCC cells by affecting YAP signaling transduction. In conclusion, we demonstrated that AMOTL2/YAP signaling is associated with MEF2D-related HCC progression. Luteolin is a promising anti-HCC compound for regulating this signaling.