OLFM4 Enhances STAT3 Activation and Promotes Tumor Progression by Inhibiting GRIM19 Expression in Human Hepatocellular Carcinoma

摘要: Olfactomedin 4 (OLFM4) induces signal transducer and activator of transcription 3 (STAT3) activation by inhibiting gene associated with retinoid-interferon-induced mortality 19 (GRIM19), a strong STAT3 suppressor gene; however, the mechanisms OLFM4 for regulating GRIM19-STAT3 cascade in hepatocellular carcinoma (HCC) remain unclear. The functions regulations OLFM4, GRIM19, HCC progression were evaluated using surgical specimens collected from 111 patients or 2 cell lines vitro. Moreover, cancer stem cell-like property mediated leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), known as an intestinal marker, was investigated. increased compared adjacent liver tissue. multivariate analysis revealed that high expression independent factor poor prognosis. negatively correlated GRIM19 positively HCC, thereby increasing cycle progression. knockdown cells inhibited activation; after double decreased again. apoptosis, proliferation, suppressed cells. incidence hematogenous recurrence higher expression, suggesting anoikis resistance enhanced OLFM4. In clinical cases, LGR5 CD133 leading to patient vitro, up-regulating through Wnt signaling pathway. Conclusion: is induced LGR5-Wnt pathway strongly aggressive tumor prognosis STAT3-induced proliferation property. Therefore, novel prognostic predictor potential therapeutic target HCC.