GSE120141
MenSCs inhibit HCC growth through oncogenic pathway suppression via regulating 5-hmC in enhancer elements [hMeDIP-seq]
We utilize MeDIP-seq, hMeDIP-seq and RNA-seq technologies to explore the epigenetic alterations in HCC after MenSC therapy. We provide distinct epigenetic landscapes of HCC cells mediated by MenSCs and demonstrate that MenSCs exert anticancer functions by regulating 5-hmC and 5-mC abundance in enhancer and promoter regions of oncogenic pathways. Deactivation of PI3K/AKT and RAF/ERK signaling attenuated the inhibition of FOXO3 and promoted downstream apoptosis. Moreover, an increase in PTEN further strengthened the suppressive effect on PI3K/AKT. Additionally, inactivation of phosphorylated ERK repressed c-myc-mediated EMT. Taken together, our results provided important epigenetic evidence for clarifying the mechanism of crosstalk between cancer and MSCs in the microenvironment and screening effective epigenetic targets for future therapy strategies based on modified MSCs. Overall design: 5-hmC, 5-mC profiles of HCC cells after MenSC therapy