Ferroptosis is an iron‐dependent mode of non‐apoptotic cell death characterized by accumulation of lipid reactive oxygen species (ROS). As a regulator of ROS, cytoglobin (CYGB) plays an important role in oxygen homeostasis and acts as a tumour suppressor. However, the mechanism by which CYGB regulates cell death is largely unknown. Here, we show that CYGB overexpression increased ROS accumulation and disrupted mitochondrial function as determined by the oxygen consumption rate and membrane potential. Importantly, ferroptotic features with accumulated lipid ROS and malondialdehyde were observed in CYGB‐overexpressing colorectal cancer cells. Moreover, CYGB significantly increased the sensitivity of cancer cells to RSL3‐ and erastin‐induced ferroptotic cell death. Mechanically, both YAP1 and p53 were significantly increased based on the RNA sequencing. The knock‐down of YAP1 alleviated production of lipid ROS and sensitivity to ferroptosis in CYGB overexpressed cells. Furthermore, YAP1 was identified to be inhibited by p53 knock‐down. Finally, high expression level of CYGB had the close correlation with key genes YAP1 and ACSL4 in ferroptosis pathway in colon cancer based on analysis from TCGA data. Collectively, our results demonstrated a novel tumour suppressor role of CYGB through p53‐YAP1 axis in regulating ferroptosis and suggested a potential therapeutic approach for colon cancer.

Gastric cancer is one of the most common malignant diseases and has one of the highest mortality rates worldwide. Its molecular mechanisms are poorly understood. Recently, the functions of non-coding RNAs (ncRNAs) in gastric cancer have attracted wide attention. Although the expression levels of various ncRNAs are different, they may work together in a network and contribute to gastric carcinogenesis by altering the expression of oncogenes or tumor suppressor genes. They affect the cell cycle, apoptosis, motility, invasion, and metastasis. Dysregulated microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), including miR-21, miR-106, H19, and ANRIL, directly or indirectly regulate carcinogenic factors or signaling pathways such as PTEN, CDK, caspase, E-cadherin, Akt, and P53. Greater recognition of the roles of miRNAs and lncRNAs in gastric carcinogenesis can provide new insight into the mechanisms of tumor development and identify targets for anticancer drug development.

A previous meta-analysis suggested no association between fish consumption and risk of pancreatic cancer. As several prospective studies with a large number of pancreatic cancer cases have emerged after that meta-analysis, we updated the evidence and examined the relationship in greater depth. We performed a literature search on PubMed and EMBASE databases through March 30, 2019 to identify potentially eligible studies. We used a random-effects model to compute summary relative risk (RR) with corresponding 95% confidence interval (CI). A total of 13 prospective studies comprising 4994 pancreatic cancer cases and 1,794,601 participants were included in the final analyses. Results of the meta-analysis showed that fish consumption was not significantly associated with risk of pancreatic cancer (RR 50-g/day = 1.03, 95% CI: 0.95–1.12), which was confirmed when stratifying the analysis by various methodological and population characteristics. There was a suggestion of difference by adjustment for family history of pancreatic cancer ( P difference = 0.05), with fish consumption being associated with higher risk of pancreatic cancer in studies without adjustment for participants’ family history (RR 50-g/day = 1.09, 95% CI: 1.02–1.18), and a non-significant inverse association among studies with the adjustment (RR 50-g/day = 0.93, 95% CI: 0.82–1.05). Results of this updated meta-analysis suggest that fish consumption is unlikely to be substantially associated with risk of pancreatic cancer.

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Carbonic anhydrase IV (CA4) is silenced in colorectal cancer. However, the effect of CA4 on the development of gastric cancer (GC) is poorly understood. The present study aimed to determine the role of CA4 in GC tumorigenesis and its underlying molecular mechanism. The levels of CA4 in GC cells and tissues were evaluated by reverse transcription-quantitative PCR and immunohistochemistry. CA4 expression was suppressed in GC cells and tissues compared with adjacent healthy tissues and normal human gastric epithelial cells, respectively. This reduced expression was significantly associated with tumor size, invasion and differentiation. Analyses with a real-time cell analyzer and clonogenic assays were conducted to validate the impact of CA4 on GC cell lines (AGS and HGC-27) and normal human gastric epithelial cell line (GES-1) proliferation. The effects of CA4 on the cell cycle in GC cells were determined by flow cytometry. The levels of CA4 and cell cycle-associated proteins were confirmed by western blotting. CA4 overexpression inhibited GC cell proliferation and reduced colony-forming ability, arrested the cell cycle in the G2/M phase, inhibited cyclin B1 and cyclin-dependent kinase 2 expression and induced p21 expression. These results indicate that CA4 may serve an important role in GC tumorigenesis by inhibiting cellular proliferation via regulating the expression of cell cycle-associated proteins. CA4 may serve as a diagnostic biomarker and a potential therapeutic target in GC.