Summary
Over-expression of Fas ligand (FasL) on tumor cell surface can induce the apoptosis of specific 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 promoting 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 target 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 cell lines, FasL expression level in MCF-7 cells was the highest, while miR-21 was down-regulated the most 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 1:1, the 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 associated 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 tumor immune privilege.
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References
Strand S, Hofmann WJ, Hug H, et al. Lymphocyte apoptosis induced by CD 95 (APO-1/Fas) ligand-expressing tumor cells—a mechanism of immune evasion? Nat Med, 1996,2(12):1361–1366
Ryan AE, Shanahan F, O’Connell J, et al. Fas ligand promotes tumor immune evasion of colon cancer in vivo. Cell Cycle, 2006,5(3):246–249
Müschen M, Moers C, Warskulat U, et al. CD95 ligand expression as a mechanism of immune escape in breast cancer. Immunology, 2000,99(1):69–77
Reimer T, Herrnring C, Koczan D, et al. FasL:Fas ratio—a prognostic factor in breast carcinomas. Cancer Res, 2000,60(4):822–828
O’Connell J, Bennett MW, O’Sullivan GC, et al. The Fas counterattack: cancer as a site of immune privilege. Immunol Today, 1999,20(1):46–52
Griffith TS, Brunner T, Fletcher SM, et al. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science, 1995,270(5239):1189–1192
Ungefroren H, Voss M, Jansen M, et al. Human pancreatic adenocarcinomas express Fas and Fas ligand yet are resistant to Fas-mediated apoptosis. Cancer Res, 1998,58(8):1741–1749
Zhang W, Ding EX, Wang Q, et al. Fas ligand expression in colon cancer: a possible mechanism of tumor immune privilege. World J Gastroenterol, 2005, 11(23):3632–3635
Sayed D, He M, Hong C, et al. MicroRNA-21 is a downstream effector of AKT that mediates its antiapoptotic effects via suppression of Fas ligand. J Biol Chem, 2011,285(26):20281–20290
Sayed D, Rane S, Lypowy J, et al. MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths. Mol Biol Cell, 2008,19(8):3272–3278
Chao TF, Xiong HH, Liu W, et al. MiR-21 mediates the radiation resistance of glioblastoma cells by regulating PDCD4 and hMSH2. J Huazhong Univ Sci Technol [Med Sci], 2013,33(4):525–552
Wang X, Liu Y, Chen X, et al. Impact of MiR-21 on the expression of FasL in the presence of TGF-β1. Aesthet Surg J, 2013,33(8):1186–1198
Wang N, Zhang CQ, He JH, et al. MiR-21 down-regulation suppresses cell growth, invasion and induces cell apoptosis by targeting FASL, TIMP3, and RECK genes in esophageal carcinoma. Dig Dis Sci, 2013,58(7):1863–1870
Wang P, Zhuang L, Zhang J, et al. The serum miR-21 level serves as a predictor for the chemosensitivity of advanced pancreatic cancer, and miR-21 expression confers chemoresistance by targeting FasL. Mol Oncol, 2013,7(3): 334–345
Zhang L, Dong LY, Li YJ, et al. miR-21 represses FasL in microglia and protects against microglia-mediated neuronal cell death following hypoxia/ischemia. Glia, 2012,60(12):1888–1895
Buscaglia LE, Li Y. Apoptosis and the target genes of microRNA-21. Chin J Cancer, 2011,30(6):371–380
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This project was supported by grants from the National Natural Science Foundation of China (No. 81172467) and the Natural Science Foundation of Hubei Province (No. 2012FFB02509).
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Wu, Mf., Yang, J., Xiang, T. et al. miR-21 targets Fas ligand-mediated apoptosis in breast cancer cell line MCF-7. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 34, 190–194 (2014). https://doi.org/10.1007/s11596-014-1257-5
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DOI: https://doi.org/10.1007/s11596-014-1257-5