| Experiment ID | EXP00172 |
| Reference | Title: The oncogene metadherin modulates the apoptotic pathway based on the tumornecrosis factor superfamily member TRAIL (Tumor Necrosis Factor-relatedApoptosis-inducing Ligand) in breast cancer. Author: Zhang N, Wang X, Huo Q, Li X, Wang H, Schneider P, Hu G, Yang Q. Journal: J Biol Chem. 2013 Mar 29;288(13):9396-407. doi: 10.1074/jbc.M112.395913. Epub2013 Feb 13. Abstract: Metadherin (MTDH), the newly discovered gene, is overexpressed in more than 40%of breast cancers. Recent studies have revealed that MTDH favors an oncogeniccourse and chemoresistance. With a number of breast cancer cell lines and breast tumor samples, we found that the relative expression of MTDH correlated withtumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity inbreast cancer. In this study, we found that knockdown of endogenous MTDH cellssensitized the MDA-MB-231 cells to TRAIL-induced apoptosis both in vitro and invivo. Conversely, stable overexpression of MTDH in MCF-7 cells enhanced cellsurvival with TRAIL treatment. Mechanically, MTDH down-regulated caspase-8,decreased caspase-8 recruitment into the TRAIL death-inducing signaling complex, decreased caspase-3 and poly(ADP-ribose) polymerase-2 processing, increased Bcl-2expression, and stimulated TRAIL-induced Akt phosphorylation, without alteringdeath receptor status. In MDA-MB-231 breast cancer cells, sensitization to TRAIL upon MTDH down-regulation was inhibited by the caspase inhibitor Z-VAD-fmk(benzyloxycarbonyl-VAD-fluoromethyl ketone), suggesting that MTDH depletionstimulates activation of caspases. In MCF-7 breast cancer cells, resistance toTRAIL upon MTDH overexpression was abrogated by depletion of Bcl-2, suggestingthat MTDH-induced Bcl-2 expression contributes to TRAIL resistance. We furtherconfirmed that MTDH may control Bcl-2 expression partly by suppressing miR-16.Collectively, our results point to a protective function of MTDH againstTRAIL-induced death, whereby it inhibits the intrinsic apoptosis pathway through miR-16-mediated Bcl-2 up-regulation and the extrinsic apoptosis pathway throughcaspase-8 down-regulation. PMID: 23408429 |
| Expressiion Profile | Description: microRNA profile of human nasopharyngeal tissues: nasopharyngeal carcinoma tissues vs. normal nasopharyngeal tissues Organism: Homo sapiens GEO ID: GSE32960 Platform: GPL14722 Number of samples: 330 |
| Design and Sample | Cancer Type: nasopharyngeal cancer Cancer SubType: N/D Cell Line: N/D Experimental Design: high grade vs low grade Case Sample: nasopharyngeal carcinoma grade 3 Control Sample: nasopharyngeal carcinoma grade 1 Num of Case: 91 Num of Control: 12 Quantification Software: Limma Num of miRNAs: 872 |
| Identification | Num of Up: 1 Num of Down: 0 |