[Show abstract][Hide abstract] ABSTRACT: The role of miR-26a in carcinogenesis appears to be a complicated one, in the sense that both oncogenic and tumor suppressive
effects were reported in cancers such as glioblastoma and hepatocellular carcinoma, respectively. Here, we report for the
first time that miR-26a is downregulated in breast cancer specimens and cell lines and its transient transfection initiates
apoptosis of breast cancer cell line MCF7 cells. Furthermore, retrovirus-delivered miR-26a impairs the in vitro colony forming and in vivo tumor-loading ability of MCF7 cells. Subsequently, MTDH and EZH2 are identified as two direct targets of miR-26a and they
are significantly upregulated in breast cancer. MCF7 xenografts with exogenous miR-26a show that a decrease in expression
of both MTDH and EZH2 is accompanied by an increase in apoptosis. Moreover, knockdown of MTDH causes apoptosis while reexpression
of MTDH partially reverses the proapoptotic effect of miR-26a in MCF7 cells. Our findings suggest that miR-26a functionally
antagonizes human breast carcinogenesis by targeting MTDH and EZH2.