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  • miR-17-92 functions as an oncogene and modulates NF-κB signaling by targeting TRAF3 in MGC-803 human gastric cancer cells.

miR-17-92 functions as an oncogene and modulates NF-κB signaling by targeting TRAF3 in MGC-803 human gastric cancer cells.

International journal of oncology (2018-09-19)
Fei Liu, Li Cheng, Jingjing Xu, Feng Guo, Weichang Chen
ABSTRACT

The miR-17-92 cluster plays either an oncogenic or anti-oncogenic role in cancer progression in diverse human cancers. However, the underlying mechanisms of the miR-17-92 cluster in gastric cancer have not yet been fully elucidated. In this study, the function of the miR-17-92 cluster in diverse aspects of MGC-803 gastric cancer cells was systematically elucidated. The enforced introduction of the miR-17-92 cluster into the MGC-803 cells significantly promoted cell growth due to the increased cellular proliferation and decreased cellular apoptosis, which were detected by CCK-8, cell viability and TUNEL assays. Moreover, the results of western blot analyses revealed that the activated protein kinase B (AKT), extracellular-signal-regulated kinase (ERK) and nuclear factor (NF-κB) signaling pathways were activated in these processes. Moreover, the overexpression of the miR-17-92 cluster markedly enhanced the migratory and invasive abilities of the MGC-803 cells, which was associated with the occurrence of epithelial-mesenchymal transition (EMT). Tumor necrosis factor receptor associated factor 3 (TRAF3), which negatively regulates the NF-κB signaling pathway, was identified as a direct target of miR-17-92. Furthermore, TRAF3 silencing enhanced the oncogenic functions of the miR-17-92 cluster in the MGC-803 cells, including the increased cellular proliferation, migration and invasion. Moreover, immunohistochemical staining and survival analyses of a gastric cancer tissue microarray revealed that TRAF3 functioned as a tumor suppressor in gastric cancer. Taken together, the findings of this study provide new insight into the specific biological functions of the miR-17-92 cluster in gastric cancer progression by directly targeting TRAF3.

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G 418 disulfate salt, powder, BioReagent, suitable for cell culture