Cytochrome C Oxidase Assembly Factor 1 Homolog Predicts Poor Prognosis and Promotes Cell Proliferation in Colorectal Cancer by Regulating PI3K/AKT Signaling.

PURPOSE: Colorectal cancer (CRC) is one of the most common malignancies in the world. The prognosis of advanced CRC is still poor. The purpose of this study was to identify a gene expression profile associated with CRC that may contribute to the early diagnosis of CRC and improve patient prognosis. PATIENTS AND METHODS: Five pairs of CRC tissues and paracancerous tissues were used to identify causative genes using microarray assays. The prognostic value of Cytochrome C Oxidase Assembly Factor 1 Homolog (COA1) in CRC was assessed in 90 CRC patients. Loss-of-function assays, cell proliferation assays using Celigo and MTT, colony formation assays, a subcutaneous xenograft mouse model, and apoptosis assays were used to define the effects of downregulation of COA1 in CRC cells in vitro and in vivo. The underlying molecular mechanisms of COA1 in CRC were also investigated. RESULTS: The causative gene COA1 was identified through microarray analysis. COA1 expression in CRC was notably associated with pathologic differentiation, tumor size, and tumor depth. COA1 expression may act as an independent prognostic factor for overall survival of CRC. Knockdown of COA1 inhibited the proliferation of CRC cells in vitro and the tumorigenicity of CRC cells in vivo. Decreased COA1 expression induced apoptosis of CRC cells. Based on the microarray assay results comparing HCT116 cells transfected with lentivirus encoding anti-COA1 shRNA or negative control shRNA, ingenuity pathway analysis (IPA) revealed that the PI3K/AKT signaling pathway was significantly enriched. Moreover, CCND1, mTOR, AKT1, and MDM2 were identified as the downstream genes of COA1. CONCLUSION: These findings demonstrate that COA1 promotes CRC cell proliferation and inhibits apoptosis by regulating the PI3K/AKT signaling pathway. Our results implicate COA1 as a potential oncogene involved in tumor growth and progression of CRC.

Evaluation of TAZ expression and its effect on tumor invasion and metastasis in human glioma.

OBJECTIVES: To evaluate the expression of TAZ and its role in tumor invasion and metastasis in human glioma. METHODS: The expression of TAZ protein was measured in 48 samples of surgically resected human glioma and 13 samples of normal brain tissues using immunohistochemistry. TAZ was knocked down by a retrovirus-mediated TAZ shRNA in a glioma cell line, SNB19. Transwell cell migration and invasion assays were used to determine migration and invasion of SNB19 cells. RESULTS: The positive expression rate of TAZ protein in glioma tissues was significantly higher than that in normal brain tissues (79.2% vs. 15.4%, P<0.001). Furthermore, clinical analysis suggested that the positive expression rate of TAZ protein in poorly differentiated tumor tissues was significantly higher as compared with that in well differentiated tissues (96.0% vs. 60.9%, P<0.01). TAZ was significantly knocked down by TAZ shRNA (P<0.001), and TAZ knockdown significantly reduced cell migration and invasion (P<0.01, respectively) in SNB19 cells. CONCLUSIONS: TAZ protein overexpression is observed in human glioma and its elevated expression is significantly correlated with poor differentiation. TAZ knockdown prominently reduces cell migration and invasion in SNB19 cells, suggesting that TAZ may play a key role in the initiation and progression of human glioma.

Mechanisms of hepatic ischemia-reperfusion injury and protective effects of nitric oxide.

Hepatic ischemia-reperfusion injury (IRI) is a pathophysiological event post liver surgery or transplantation and significantly influences the prognosis of liver function. The mechanisms of IRI remain unclear, and effective methods are lacking for the prevention and therapy of IRI. Several factors/pathways have been implicated in the hepatic IRI process, including anaerobic metabolism, mitochondria, oxidative stress, intracellular calcium overload, liver Kupffer cells and neutrophils, and cytokines and chemokines. The role of nitric oxide (NO) in protecting against liver IRI has recently been reported. NO has been found to attenuate liver IRI through various mechanisms including reducing hepatocellular apoptosis, decreasing oxidative stress and leukocyte adhesion, increasing microcirculatory flow, and enhancing mitochondrial function. The purpose of this review is to provide insights into the mechanisms of liver IRI, indicating the potential protective factors/pathways that may help to improve therapeutic regimens for controlling hepatic IRI during liver surgery, and the potential therapeutic role of NO in liver IRI.