An analysis of the expression and function of myeloid differentiation factor 88 in human osteosarcoma

Abstract

The aim of the present study was to investigate the expression and function of myeloid differentiation factor 88 (MyD88) in osteosarcoma. Immunohistochemical staining was used to detect MyD88 protein in osteosarcoma tissues and matched normal bone tissues. The association between MyD88 expression and the clinical characteristics of patients with osteosarcoma was analyzed. Furthermore, survival analysis of patients with osteosarcoma was performed to study the association between MyD88 expression and patient prognosis. Finally, the effect of the MyD88 inhibitor, ST2825, on the proliferation and apoptosis of the human osteosarcoma cell line U2OS was examined. Additionally, cell proliferation, invasion and apoptosis were examined using an MTT assay, Transwell assay and Annexin V-fluorescein isothiocyanate staining kit, respectively. The expression of proteins associated with the NF-κB signaling pathway was analyzed by western blotting. The positive expression rate of MyD88 in osteosarcoma and normal bone tissues was 71.4 and 6.1%, respectively. Statistical analysis demonstrated that MyD88 was not associated with gender, age, histological type or tumor location, but that it was associated with Enneking stage and tumor metastasis (P<0.05). According to the survival analysis, patients with osteosarcoma in the high MyD88 expression group displayed a reduced overall survival rate (P<0.05). Furthermore, inhibition of MyD88 by ST2825 in U2OS cells resulted in a marked decrease in cellular proliferation and migration, and an increase in the rate of apoptosis (P<0.05). Notably, ST2825 significantly decreased cyclin D1, matrix metallopeptidase-9 and nucleus p65 expression, but increased cleaved-caspase 3 expression in ST2825-treated U2OS cells (P<0.05). The results of the present study indicated that MyD88 expression is associated with the progression of osteosarcoma and may be a potential therapeutic target for the treatment of osteosarcoma.

Myeloid Differentiation Primary Response 88–Cyclin D1 Signaling in Breast Cancer Cells Regulates Toll-Like Receptor 3-Mediated Cell Proliferation

“…Though MyD88 does not have any catalytic activity, its activation causes dimerization leading to the activation of downstream kinases (10). It has been shown that the progression of signaling pathways occur due to the phosphorylation of two key adaptor proteins IRAK1 and TAK1.…”

“…Canonical TLR signaling has been reported to be regulated by an array of molecules through various mechanisms to adjust the consequences of associated autoimmune and inflammatory diseases. In the canonical pathway, for most of the TLRs, upon ligand activation, MyD88 is recruited as a dimer in the cytoplasmic TIR domain in a homophilic interaction (10)(11)(12)(13)(14)(15).…”

Alternative MyD88 -Cyclin D1 signaling in breast cancer cells regulates TLR3 mediated cell proliferation

“…Though, MyD88 does not have any catalytic activity, its activation causes dimerization leading to the activation of downstream kinases (Chen et al, 2018). It has been shown that the progression of signaling pathways occur due to the phosphorylation of two key adaptor proteins IRAK1 and TAK1.…”

“…Canonical TLR signaling has been reported to be regulated by an array of molecules through various mechanisms to adjust the consequences of associated autoimmune and inflammatory diseases. In the canonical pathway, for most of the TLRs, upon ligand activation, MyD88 recruited as a dimer in the cytoplasmic TIR domain in a homophilic interaction (Chen et al, 2018; Loiarro et al, 2010; Noursadeghi et al, 2008; Jia et al, 2014; Hsiao et al, 2014; Han et al, 2002).…”

ST2825, independent of MyD88, induces reactive oxygen species-dependent apoptosis in multiple myeloma cells

“…That resulted in the inhibition of interleukin 1 beta-mediated activation of NF-κB activity [ 11 ]. Preclinical studies have demonstrated the antitumor activity of ST2825 in multiple types of malignancies such as lymphoma, leukemia, and osteosarcoma [ 12 , 13 ]. However, neither the pathological role of MyD88 nor the treatment effect of ST2825 is currently under investigation in MM.…”