CHFR promotes metastasis of human gastric carcinoma by activating AKT and ERK via NRF2- ROS axis.

Tumor suppressor gene CHFR (The Checkpoint with Forkhead-associated and Ring finger domains) is a mitotic checkpoint and frequently hypermethylated in gastric cancer. Our previous study found CHFR played a certain extent pro-tumor function in gastric cancer. However, little is known about the underlying mechanism. In this study, we tried to further elucidate the role and mechanism for CHFR in gastric cancer (GC) by constructing CHFR stably expressed cell lines. As expected, the ectopic expression of CHFR slowed the cell proliferation in both two SGC-7901 and AGS cells, while significantly promoted the potential of cell migration and invasion. For the first time, our data indicated that stable expression of CHFR in SGC-7901 and AGS restrained cellular reactive oxygen species (ROS) generation and promoted the activation of AKT and ERK, two regulators of redox hemostasis. Furthermore, H2O2 treatment effectively elevated ROS level and reversed CHFR-induced cell invasion in stable SGC-7901 and AGS cells with the decreased phosphorylation of AKT and ERK. We also confirmed that CHFR exerted its function by promoting NRF2 expression. The most important is, the ectopic expression of CHFR significantly inhibited SGC-7901 cell-derived xenografts and obviously promoted lung metastasis of GC cell with NRF2, p-AKT and p-ERK increased. Taken together, our findings suggested that CHFR might take part in gastric cancer progression especially cancer metastasis by activating AKT and ERK via NRF2- ROS axis.

CHFR promotes the migration of human gastric cancer cells by inducing epithelial-to-mesenchymal transition in a HDAC1-dependent manner.

BACKGROUND: Previous studies have illustrated that checkpoint with forkhead-associated and ring finger domains (CHFR) was frequently silenced in several cancer types due to promoter hypermethylation and functions as a tumor suppressor gene. However, the data from the public dataset reveal that CHFR is highly expressed in human gastric cancer specimens, and the biological function of CHFR in gastric cancer is still not well understood. MATERIALS AND METHODS: The clinical association between CHFR expression and the overall survival of gastric cancer patients as well as cancer metastasis was analyzed according to public datasets. The CHFR expression in clinical specimens and human gastric cancer cell lines was detected by immunohistochemistry and Western blotting, respectively. Gain (overexpression) and loss (silencing) of function experiments were used to elucidate the role of CHFR in gastric cancer. The migration ability of gastric cancer cells was determined by wound healing and transwell assays. Cell cycle distribution was analyzed using fluorescence-activated cell sorting experiment. The expression of the proteins in cancer cells was measured using Western blot analysis. RESULTS: According to the analysis from Kaplan-Meier plotter dataset, CHFR expression was negatively associated with overall survival of gastric cancer patients. Our data revealed that exogenous expression of CHFR not only arrested cell cycle but also led to dramatically enhanced cell migration, while silencing of CHFR significantly inhibited cell migration in gastric cancer cells. This result is consistent with the data from the Human Cancer Metastasis Dataset, in which CHFR level is found to significantly increase in metastatic gastric cancer. The overexpression of CHFR promoted epithelial-mesenchymal transition (EMT) in both SGC-7901 and AGS cells, while HDAC1 was inhibited. Interestingly, suberoylanilide hydroxamic acid, a HDAC1 antagonist, could effectively increase cell migration in both cell lines via enhancement of EMT. CONCLUSION: Our data indicated that CHFR exerted positive effects on cell migration of human gastric cancer by promoting EMT via downregulating HDAC1.

Study on the influence of assistant experience on the quality of colonoscopy: A pilot single-center study.

BACKGROUND AND OBJECTIVE: Colonoscopy is the most important method for the diagnosis and treatment of intestinal diseases, and there are many factors affecting the quality of examination. Although the assistant is one of the factors influencing the quality of colonoscopy, there are few studies on the effect of different assistants with different experiences on the quality of colonoscopy. Therefore, the study was aimed to research the correlation between different assistants with different experiences and the quality of water-injection colonoscopy. METHOD: In this study, a single-center randomized controlled trial was conducted to analyze the key quality indicators (the rate to arrive cecum, time to arrive cecum, total operation time, detection rate of polyps, detection rate of adenoma, pain score, operation satisfaction, and the pressure on abdomen) of patients who underwent water-injection colonoscopy under non-sedation from January 2018 to June 2018 in the center. Patients were randomly assigned to different assistant groups based on the actual working period of 6 months (0∼6 months inexperienced assistant group and assistant group with more than 6 months of experience). Through fitting the bivariate and multivariate logistic regression models, the differences between the two groups and the effects on the key quality indicators of colon examination were analyzed. RESULTS: A total of 331 patients who were eligible for non-sedation colonoscopy were randomly assigned to the experienced assistant group (n = 179) and the inexperienced assistant group (n = 152). Among them, 103 cases of polyp and 70 cases of adenoma were detected. The rate to arrive cecum, polyp detection rate and adenoma detection rate were compared between the two groups during operation (P > 0.05). However, there were significant differences in the time to arrive cecum, patients' satisfaction with operation, pain score and abdominal pressure (P < .05). In the inexperienced assistant group, 20% of the operation time was one standard deviation higher than the mean value, while the experienced assistant group was 12% (339 s vs 405s, OR 0.541, 95% 0.295-0.990). Compared with the inexperienced assistant group, patients in the experienced assistant group had higher operational satisfaction (98.32% vs 92.11%, OR 0.199, 95% 0.055-0.718) and lower pain score (0.3 vs 0.49, OR 1.993, 95% 1.52-3.775). All relations remained unchanged after adjusting for potential confounders. CONCLUSION: The assistant is a key factor in the quality of colonoscopy, especially in the case of non-sedating colonoscopy. The experience of the assistant is related to the time to arrive cecum, the degree of pain and the overall satisfaction of patient with the operation. The assistant should be subject to the quality supervision of the endoscopic inspector. Proof of human Clinical Trial Registration: The institutional review board of Fifth Affiliated Hospital of Wenzhou Medical College, Zhejiang Province, China approved the study. The study is registered on. Chinese Clinical Trial Registry (ChiCTR1800015650).

Association between CHFR gene hypermethylation and gastric cancer risk: a meta-analysis.

BACKGROUND: The association between the hypermethylation of CHFR gene and gastric cancer risk has been investigated by a number of studies. However, the sample size of the majority of these studies was very small. To get a more a convincing conclusion, here we performed a meta-analysis of the previously published studies to assess the association between CHFR methylation and the risk of gastric cancer. METHODS: Eligible studies were identified by searching the MEDLINE/PubMed, Embase, and Web of Science databases before May 2016 without any language restriction. The strength of the association was estimated by odds ratio with its 95% confidence interval (CI). RESULTS: Totally 1,399 samples, including 758 gastric cancer cases and 641 controls, from 13 studies were included in the present meta-analysis. Compared with non-cancer controls, the pooled OR of CHFR methylation in gastric cancer patients was 9.08 (95% CI: 6.40-12.88, P<0.001), suggesting that the methylation of CHFR was significantly associated with increased risk of gastric cancer. Similar results were observed when subgroup analyses were performed stratified by country, ethnicity, and methylation testing methods. CONCLUSION: Our meta-analysis showed a strong positive correlation between CHFR methylation and risk of gastric cancer, suggesting that CHFR methylation might be a promising biomarker for the diagnosis of gastric cancer.