ABSTRACT
INTRODUCTION AND OBJECTIVES: Warburg effect is attracting increasing attention as it is important for cancer progression. However, how cancer cells regulate glucose metabolism through glycolysis is still unknown. Here, we demonstrated the regulatory role of Ras related GTP binding D (RRAGD) in human hepatocellular carcinoma (HCC) cells. PATIENTS OR MATERIALS AND METHODS: Kaplan-Meier's analysis was used to analyze the correlation between RRAGD expression levels and prognosis of HCC patients from the Cancer Genome Atlas database. Two stable RRAGD knockdown HCC cell lines were created using shRNAs to investigate cancer progression and aerobic glycolysis. Western blot and quantitative reverse transcription polymerase chain reaction were performed to detect the expression levels of RRAGD and MYC. RESULTS: RRAGD expression was elevated in HCC patients with poor prognosis. RRAGD knockdown could inhibit the proliferation, invasion and migration of Huh-7 and HepG2 cells. Interestingly, silence RRAGD was able to reduce the glucose uptake, lactate production and extracellular acidification rate of HCC. RRAGD expression level was up-regulated by oncogene MYC in HCC cells. CONCLUSION: This study highlights RRAGD as an important cancer-promoting factor for cancer progression and aerobic glycolysis, and thereby it is a potential therapeutic target for HCC intervention.
Subject(s)
Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Monomeric GTP-Binding Proteins/genetics , Warburg Effect, Oncologic , Carcinoma, Hepatocellular/metabolism , Cell Culture Techniques , Cell Line, Tumor , Databases, Factual , Humans , Liver Neoplasms/metabolism , Monomeric GTP-Binding Proteins/metabolism , Prognosis , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , RNA, Messenger/metabolismABSTRACT
OBJECTIVE: The aim of this study was to investigate the expression of FXYD domain-containing ion transport regulator 6 (FXYD6) mRNA and protein in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) tissues with cirrhosis, the corresponding paracancerous tissues and the normal liver tissues, and to explore the clinical significance of FXYD6 expression in HBV-related HCC with cirrhosis. METHODS: The FXYD6 mRNA and protein were examined by semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively. RESULTS: The FXYD6 mRNA in HBV-related HCC tissues was significantly higher than that in the cirrhosis tissues or that in the normal liver tissues. The positive expression rate of FXYD6 protein was statistically higher in HBV-related HCC tissues than that in HBV-related cirrhosis or that in normal liver tissues. There was no significant correlation between the expression of FXYD6 protein and gender, age, histological differentiation, tumor diameter, tumor number, integrity of tumor capsule or not and alpha fetoprotein (AFP) concentration in serum, but the protein expression was associated with microvascular invasion, pathological stage, and early recurrence after operation within 1 year. CONCLUSION: FXYD6 might be involved in hepatocyte carcinogenesis and tumor progression in HBV-related HCC with cirrhosis and indicated a poor prognosis.
