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TRIM56 Suppresses Multiple Myeloma Progression by Activating TLR3/TRIF Signaling
Yonsei Medical Journal ; : 43-50, 2018.
Article in English | WPRIM | ID: wpr-742506
ABSTRACT

PURPOSE:

Tripartite-motif-containing protein 56 (TRIM56) has been found to exhibit a broad antiviral activity, depending upon E3 ligase activity. Here, we attempted to evaluate the function of TRIM56 in multiple myeloma (MM) and its underlying molecular basis. MATERIALS AND

METHODS:

TRIM56 expression at the mRNA and protein level was measured by qRT PCR and western blot analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry analysis was performed to investigate the effect of TRIM56 on MM cell proliferation and apoptosis. The concentrations of interferon (IFN)-β, interleukin (IL)-6, and tumor necrosis factor-α in MM cell culture supernatants were detected with respective commercial ELISA kits. Western blot was employed to determine the effect of TRIM56 on toll-like receptor 3 (TLR3)/toll-IL-1 receptor (TIR) domain-containing adaptor inducing IFN-β (TRIF) signaling pathway.

RESULTS:

TRIM56 expression was prominently decreased in MM cells. Poly (dAdT)-induced TRIM56 overexpression in U266 cells suppressed proliferation, induced apoptosis, and enhanced inflammatory cytokine production, while TRIM56 knockdown improved growth, diminished apoptosis, and inhibited inflammatory cytokine secretion in RPMI8226 cells. Moreover, TRIM56 knockdown blocked TLR3 signaling pathway. Furthermore, poly (IC), a TLR3 agonist, markedly abolished TRIM56 depletion-induced increase of proliferation, decrease of apoptosis, and reduction of inflammatory factor in MM cells.

CONCLUSION:

TRIM56 may act as a tumor suppressor in MM through activation of TLR3/TRIF signaling pathway, contributing to a better understanding of the molecular mechanism of TRIM56 involvement in MM pathogenesis and providing a promising therapy strategy for patients with MM.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Signal Transduction / Down-Regulation / Cytokines / Poly I-C / Apoptosis / Disease Progression / Adaptor Proteins, Vesicular Transport / Cell Line, Tumor / Ubiquitin-Protein Ligases / Cell Proliferation Limits: Humans Language: English Journal: Yonsei Medical Journal Year: 2018 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Signal Transduction / Down-Regulation / Cytokines / Poly I-C / Apoptosis / Disease Progression / Adaptor Proteins, Vesicular Transport / Cell Line, Tumor / Ubiquitin-Protein Ligases / Cell Proliferation Limits: Humans Language: English Journal: Yonsei Medical Journal Year: 2018 Type: Article