Involvement of miRMAs in the interaction between cancer stem cells and tumor micro-environment

Our investigation establishing stable clones from ESCC cell lines with induced miR-203 expression resulted in significant growth inhibition in vitro and in vivo. In p75NTR-negative cells, the expression of p63 was down-regulated and involucrin was up-regulated. Small foci were observed in mouse xenograft tumors with stratified squamous differentiation. The expression of basement membrane protein laminine was localized at the center of the foci and p75NTR-positive cells resided at the basal layer. Our cDNA microarray analysis demonstrated up-regulation of genes involved in regulating tissue polarity, such as BMP-4 and ZO-1. These results demonstrated that miR-203 regulated both self renew of CSLCs and differentiation of non-CSLCs, leading significant tumor growth inhibition with restored epithelial tissue architecture in vivo, which suggests the use of miR-203 as a novel therapeutic target for ESCC.