ABSTRACT
AIMS: To investigate the role of cIAP2 in the malignant biological behaviours of hepatocellular carcinoma (HCC) cells and determine its mechanism of action. MAIN METHODS: cIAP2 protein expression was detected via immunohistochemistry (IHC) in 102 HCC specimens and 43 paracancerous liver tissues, and its relationship with clinicopathological features and patient prognosis was analysed. Then, short interfering RNA (siRNA) technology was used to knock down cIAP2 expression in BEL7402 and HepG2 cells. Cell Counting Kit-8 (CCK8) and Transwell assays were used to determine cell proliferation and invasion after knockdown of cIAP2 expression. The relationship between cIAP2 and the NF-κB pathway was explored via western blotting (WB) and a dual luciferase reporter system. Finally, nude mouse models of liver cancer were established to detect the effect of cIAP2 on tumourigenicity and the proliferation activity of orthotopic HCC cells. KEY FINDINGS: cIAP2 expression was significantly increased in HCC tissues and was correlated with intravascular thrombosis in HCC. High cIAP2 expression was correlated with poor patient prognosis. cIAP2 knockdown significantly reduced the proliferation and invasion of BEL7402 and HepG2 cells and the activity of the NF-κB pathway. Animal experiments showed that cIAP2 knockdown reduced the tumourigenicity of HepG2 cells in the liver of nude mice and the proliferation activity of the orthotopic HCC cells. SIGNIFICANCE: cIAP2 plays an important role in HCC proliferation and invasion and may exert its effects via the NF-κB signalling pathway.
Subject(s)
Baculoviral IAP Repeat-Containing 3 Protein/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/pathology , Cell Proliferation , Liver Neoplasms/pathology , NF-kappa B/metabolism , Animals , Apoptosis , Baculoviral IAP Repeat-Containing 3 Protein/genetics , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Cell Movement , Female , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Middle Aged , NF-kappa B/genetics , Neoplasm Invasiveness , Prognosis , Survival Rate , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
Gastric cancer (GC), one of the most common cancers of the digestive system, results in high morbidity and mortality, but the molecular mechanisms underlying GC remain largely unknown. Cadherin-17 (CDH17) is a nonclassical member of the cadherin (CDH) superfamily of calcium-dependent proteins. Despite recent advances in the understanding of CDH17 biology, the mechanism of CDH17 in GC proliferation, migration, and invasion has not been extensively studied. In the present study, we observed that CDH17 expression was increased in GC tissues compared with para-carcinoma tissues and was correlated with lymph node metastasis and the AJCC stage. Additionally, a significant correlation was found between CDH17 protein expression and the number of blood and lymph vessels in GC tissues. Furthermore, in vitro suppression of CDH17 expression using short-interfering RNA (siRNA) decreased AGS cell proliferation, migration and invasion. Conversely, overexpression of CDH17 through plasmid transfection enhanced the malignant activity of AGS cells. Moreover, CDH17 increased the matrix metallopeptidase 2 (MMP-2) levels via the canonical nuclear factor-kappaB (NF-κB) pathway. Our findings offer new insights into the mechanism of the CDH17/NF-κB/MMP-2 axis, and the associated signalling pathways might represent novel targets for the treatment of GC.
