RESUMEN
Abnormal expression of miR-224 has been reported to promote cancer progression. However, the role of miR-224 is seldom reported in oral squamous cell carcinoma (OSCC). We reported that miR-224 expression was significantly down-regulated in OSCC tissues and cell lines. Restoration of miR-224 decreased OSCC cell growth and invasion. In addition, luciferase and Western blot assays revealed that ADAM17 protein was a downstream target of miR-224. The overexpression of ADAM17 dismissed miR-224's effect on cell growth and invasion. We concluded that miR-224 inhibited OSCC cell growth and invasion through regulating ADAM17 expression. Subsequently, we revealed that c-jun directly bind to miR-224 promoter and decreased miR-224 expression. Taken together, these findings demonstrated that miR-224 may function as a tumour-suppressive microRNA in OSCC and suggested that miR-224 may be a potential therapeutic target for OSCC patients.
Asunto(s)
Proteína ADAM17/genética , Carcinoma de Células Escamosas/genética , Transición Epitelial-Mesenquimal/genética , MicroARNs/metabolismo , Neoplasias de la Boca/genética , Proteína ADAM17/metabolismo , Animales , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Inmunoprecipitación de Cromatina , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Proteínas Proto-Oncogénicas c-jun/metabolismo , Trasplante HeterólogoRESUMEN
BACKGROUND: Blocking the programmed death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in hepatocellular carcinoma (HCC) is a very promising approach in immunotherapy. However, the correlation and prognostic values of serum soluble PD-1 and PD-L1 (sPD-1/sPD-L1) have not been explored conjointly in HCC patients. METHODS: This study retrospectively included 120 HCC patients receiving radical resection. The serum levels of sPD-1/sPD-L1 and inflammatory cytokines were measured by antibody array assay. Immunohistochemistry was applied to assess both the expression of membrane-bound PD-L1, and the number of CD4+ tumor-infiltrating lymphocytes (TILs) and CD8+ TILs. RESULTS: The best cut-off values of sPD-1 and sPD-L1 for predicting disease-free survival (DFS) were 33.0 µg/ml and 11.2 µg/ml, respectively. Multivariable analysis showed that sPD-L1 was a negative independent prognostic factor [DFS, Hazard Ratio (HR) 2.58, 95% CI 1.14-5.84, P = 0.023; overall survival (OS), HR 1.77, 95% CI 1.01-3.12, P = 0.048], while sPD-1 was a favorable independent prognostic factor (DFS, HR 0.32, 95% CI 0.14-0.74, P = 0.007; OS, HR 0.54, 95% CI 0.30-0.98, P = 0.044) in HCC patients. We also observed some similar associations between inflammatory cytokines (IL-10, IL-17, TNF-α) and sPD-1 or sPD-L1, as well as a close positive association between sPD-1 and sPD-L1. No significant associations of sPD-1/sPD-L1 with either intra-tumoral PD-L1 expression, or the numbers of CD4+ TILs and CD8+ TILs were determined. CONCLUSIONS: Our findings indicate that sPD-1 and sPD-L1 are independent prognostic factors with opposite prognostic roles in predicting both DFS and OS in HCC patients.