miR-21 Targets Fas Ligand-mediated Apoptosis in Breast Cancer Cell Line MCF-7

Over-expression of Fas ligand(FasL) on tumor cell surface can induce the apoptosis of spe cific activated tumor infiltrating lymphocytes(TILs) via the Fas/FasL pathway, leading to the formation of a site of immune privilege surrounding the tumor mass for escaping immune surveillance and pro moting tumor proliferation, invasion and metastasis. The blocking effect of miR-21 on FasL-mediated apoptosis in breast cancers was investigated in this study. The expression levels of miR-21 and FasL in human breast carcinoma cell lines were detected by using RT-PCR and Western blotting. FasL as a tar get gene of miR-21 was identified by Luciferase assay. The apoptosis of Jurkat T lymphocytes induced by MCF-7 cells was determined by flow cytometry. It was found that in four human breast cancer cel lines, FasL expression level in MCF-7 cells was the highest, while miR-21 was down-regulated the mos notably. After miR-21 expression in MCF-7 cells was up-regulated, FasL was identified as a target gene of miR-21. When the effector/target(E/T) ratio of MCF-7 cells and Jurkat cells was 10:1, 5:1 and 1:1the inhibitory rate of apoptosis of Jurkat T lymphocytes induced by MCF-7 cells was 95.81%, 93.16%and 91.94%, respectively. It is suggested that in breast cancers miR-21 expression is negatively associ ated with FasL expression, and FasL is a target gene of miR-21. miR-21 targeting and regulating FasL-mediated apoptosis will bring us the possibility of a new tumor immunotherapy via breaking tu mor immune privilege.