JC polyoma virus (JCPyV), a ubiquitous polyoma virus that commonly infects people, is identified as the etiologic factor for progressive multifocal leukoencephalopathy and has been closely linked to various human cancers. Transgenic mice of CAG-loxp-Laz-loxp T antigen were established. T-antigen expression was specifically activated in gastroenterological target cells with a LacZ deletion using a cre-loxp system. Gastric poorly-differentiated carcinoma was observed in T antigen-activated mice using K19-cre (stem-like cells) and PGC-cre (chief cells), but not Atp4b-cre (parietal cells) or Capn8-cre (pit cells) mice. Spontaneous hepatocellular and colorectal cancers developed in Alb-cre (hepatocytes)/T antigen and villin-cre (intestinal cells)/T antigen transgenic mice respectively. Gastric, colorectal, and breast cancers were observed in PGC-cre/T antigen mice. Pancreatic insulinoma and ductal adenocarcinoma, gastric adenoma, and duodenal cancer were detected in Pdx1-cre/T antigen mice. Alternative splicing of T antigen mRNA occurred in all target organs of these transgenic mice. Our findings suggest that JCPyV T antigen might contribute to gastroenterological carcinogenesis with respect to cell specificity. Such spontaneous tumor models provide good tools for investigating the oncogenic roles of T antigen in cancers of the digestive system.

Background Belonging to the G-protein coupled receptor 1 family, G protein-coupled receptor 176 (GPR176) is associated with the Gz/Gx G-protein subclass and is capable of decreasing cAMP production. Methods GPR176 expression was detected by qRT-PCR, bioinformatics analysis, Western blot and immunohistochemistry, and compared with clinicopathological characteristics of breast cancer. GPR176-related genes and pathways were subjected to bioinformatic analysis. We also explored the effects of GPR176 on the phenotypes of breast cancer cells. Results Lower expression of GPR176 mRNA was seen in breast cancer than in normal tissues, but the opposite pattern was found for its protein (p < 0.05). GPR176 mRNA was associated with female sex, low T staging, non-Her-2+ subtypes, non-mutant p53 status in breast cancer (p < 0.05). GPR176 methylation was negatively correlated with its mRNA level and T staging in breast cancer, and was higher in breast cancer than normal tissues (p < 0.05). GPR176 protein expression was positively correlated with older age, small tumor size, and non-luminal-B subtype of breast cancers (p < 0.05). The differential genes of GPR176 were involved in receptor-ligand interaction, RNA maturation, and so forth (p < 0.05). GPR176-related genes were categorized into cell mobility, membrane structure, and so on (p < 0.05). GPR176 knockdown weakened the proliferation, glucose catabolism, anti-apoptosis, anti-pyroptosis, migration, invasion, and epithelial-mesenchymal transition of breast cancer cells. Conclusion These results indicate that GPR176 might be involved in the tumorigenesis and subsequent progression of breast cancer by deteriorating aggressive phenotypes. It might be utilized as a potential biomarker to indicate the aggressive behaviors and poor prognosis of breast cancer and a potential target of genetic therapy.

Introduction:G-protein-coupled receptor 176 (GPR176) is a member of the G-protein coupled receptor (GPCR) 1 family and produces a 515 amino acid glycosylated protein. Materials and Methods: In the present study, GPR176 expression was detected using immunohistochemistry (IHC) and compared with clinicopathological characteristics of ovarian cancer using bioinformatics analysis. GPR176-related genes and pathways were analyzed using bioinformatics analysis. In addition, the effects of GPR176 on the phenotypes of ovarian cancer cells were investigated. Results:GPR176 mRNA expression positively correlated with older age, clinicopathological staging, tumor residual status, and unfavorable survival of ovarian cancer (p < 0.05) but negatively with purity loss, infiltration of B cells, and CD8+ T cells (p < 0.05). Gene Set Enrichment Analysis (GSEA) showed that differential expression of the GPR176 gene was involved in focal adhesion, ECM-receptor interaction, ribosome, oxidative phosphorylation, actin skeleton, cytokine-cytokine receptor interaction, gap junction, and cell adhesion molecules (p < 0.05). STRING and Cytoscape were used to determine the top 10 nodes (FN1, COL1A1, MMP2, COL1A2, COL3A1, THBS1, ACAN, DCN, COL5A1, LUM) which were downregulated in ovarian cancer (p < 0.05). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that GPR176-related genes were categorized into the AGE-RAGE signaling pathway in diabetic complication, ECM receptor interaction, protein digestion and absorption, ECM structural constituent and organization, and collagen trimer (p < 0.05). GPR176 overexpression promoted the proliferation, anti-apoptosis, anti-pyroptosis, migration and invasion of ovarian cancer cells with overexpression of N-cadherin, Zeb1, Snail, Twist1, and underexpression of gasdermin D, caspase 1, and E-cadherin. These results indicated that GPR176 might be involved in the progression of ovarian cancer by deteriorating aggressive phenotypes. Conclusion:GPR176 could potentially be used as a biomarker to indicate the aggressive behavior and poor prognosis of ovarian cancer and a target of genetic therapy.

Purpose As a member of the G-protein-coupled receptor 1 family, the G-protein-coupled receptor 176 (GPR176) gene encodes a glycosylated protein made up of 515 amino acids. The current study was performed to evaluate the impact of GPR176 on the clinicopathology and prognosis of oesophageal cancer, as well as uncover its molecular mechanisms. Methods Bioinformatics and clinical tissue samples were used to detect the expression and clinicopathological significance of GPR176 in oesophageal cancer. The expression, proliferation, migration and invasion, apoptosis and lipid droplet formation of GPR176 gene in oesophageal cancer were performed as phenotypic readouts. Results Here, RT-PCR and bioinformatic analyses revealed that GPR176 mRNA expression was significantly higher in oesophageal cancer than in normal mucosa (p < 0.05). GPR176 mRNA expression was associated with low weight and BMI, low T stage, low N and clinicopathological stage, low histological grade and favourable clinical outcome of oesophageal cancer (p < 0.05). The differential genes of GPR176 mRNA were involved in protein digestion and absorption, extracellular matrix constituent, endoplasmic reticulum lumen, among others (p < 0.05). GPR176-related genes were classified as being involved in oxidoreductase activity, actin and myosin complexes, lipid localisation and transport, among others (p < 0.05). GPR176 knockdown suppressed proliferation, anti-apoptotic and anti-pyroptotic properties, migration, invasion, chemoresistance and lipid droplet formation in oesophageal cancer cells (p < 0.05), while ACC1 and ACLY overexpression reversed the inhibitory effects of GPR176 silencing on lipid droplet formation and chemoresistance. Conclusion These findings indicated that upregulated expression of GPR176 might be involved in oesophageal carcinogenesis and subsequent progression, aggressiveness, and induced chemoresistance by ACC1- and ACLY-mediated lipogenesis and lipid droplet assembly.

FAM64A is a mitogen‐induced regulator of the metaphase and anaphase transition. Here, we found that FAM64A messenger RNA (mRNA) and protein expression levels were higher in gastric cancer tissue than in normal mucosa (p < .05). FAM64A methylation was negatively correlated with FAM64A mRNA expression (p < .05). The differentially expressed genes of FAM64A were mainly involved in digestion, potassium transporting or exchanging ATPase, contractile fibers, endopeptidase, and pancreatic secretion (p < .05). The FAM64A‐related genes were principally categorized into ubiquitin‐mediated proteolysis, cell cycle, chromosome segregation and mitosis, microtubule binding and organization, metabolism of amino acids, cytokine receptors, lipid droplet, central nervous system, and collagen trimer (p < .05). FAM64A protein expression was lower in normal gastric mucosa than intestinal metaplasia, adenoma, and primary cancer (p < .05), negatively correlated with older age, T stage, lymphatic and venous invasion, tumor, node, metastasis stage, and dedifferentiation (p < .05), and associated with a favorable overall survival of gastric cancer patients. FAM64A overexpression promoted proliferation, antiapoptosis, migration, invasion, and epithelial–mesenchymal transition via the EGFR/Akt/mTOR/NF‐κB, while the opposite effect was observed for FAM64A knockdown. FAM64A also induced chemoresistance directly or indirectly through lipid droplet formation via ING5. These results suggested that upregulation of FAM64A expression might induce aggressive phenotypes, leading to gastric carcinogenesis and its subsequent progression. Thus, FAM64A could be regarded as a prognosis biomarker and a target for gene therapy.