SMYD2 epigenetically activates BMP4/SMAD1/5/8/ID3 axis to enhance cancer stem cell properties and drive sorafenib resistance in hepatocellular carcinoma

Drug resistance prominently hampers the effects of sorafenib in HCC. Epigenetics play important roles in drug resistance. However, the contributions of SMYD2 to sorafenib resistance in HCC remain largely unknown. In this study, using our established sorafenib-resistant Huh7 cell, we performed RNA-Seq to screen to identify SMYD2 targets, and found that BMP4 is a SMYD2 target involved in CSC stemness. In summary, our data demonstrate that targeting SMYD2/BMP4 is an effective approach to overcome sorafenib resistance in HCC.