NOTCH1 and hepatocellular carcinoma: Furthermore, in sorafenib-resistant HCC cell lines, in which Notch1 and EZH2 enhance self-renewal and tumorigenicity, knockdown or pharmacological inhibition of EZH2 suppressed Notch1 signaling activity through upregulation of Notch1-related microRNAs (miR-21-5p and miR-26a-1-5p) and abrogated CSC stemness, suggesting the EZH2/Notch1 axis as a rational therapeutic target [300].