Restored expression of the tumor suppressor gene RUNX3 reduces cancer stem cells in hepatocellular carcinoma by suppressing Jagged1-Notch signaling

摘要: Runt-related transcription factor 3 (RUNX3) is a candidate tumor suppressor gene that downregulated in various cancers. In the present study, we analyzed regulatory function of RUNX3 on Jagged-1 (JAG1) expression and cancer stem cell (CSC) signaling hepatocellular carcinoma (HCC). Eleven HCC lines 30 human tissues were used. JAG1 levels by immunoblotting immunohistochemistry. Ectopic was induced introducing cDNA into RUNX3-negative line Hep3B Huh7 cells. Furthermore endogenous knocked down siRNA SK-Hep-1 order to analyze transcriptional regulation, conducted reporter assays, chromatin immunoprecipitation (ChIP) assays electrophoretic mobility shift (EMSAs). Tumorigenicity using SCID mouse liver injection model. An inverse correlation observed between most tissues. Restoring decreased cells, whereas upregulated siRNA-treated Reporter ChIP EMSAs revealed directly bound region suppressed transcription. Moreover, restoration CSCs suppressing JAG1-mediated Notch signaling. The tumorigenic capacity RUNX3-expressing cells lower compared control resulted downregulation tumorigenesis suppression CSCs.