Long-term infection with Helicobacter pylori (H. pylori) leads to elevated serum gastrin levels, which are closely related to gastric cancer. Eradication of H. pylori to treat the high gastrin levels is increasingly challenged by antibiotic resistance. Dopamine (DA) receptor 1 (D1R) is expressed on G cells in the gastric antrum. Parietal cells produce DA, which inhibits somatostatin (SOM) release through D2R on D cells in the gastric mucosa. Whether targeted intervention in DRs can improve high gastrin levels after H. pylori infection remains to be explored. In this study, human gastric tissue, H. pylori-infected mice, D1R and D2R knockout mice, RT‒qPCR, ELISA, IHC, Western Blot, HE staining and ex vivo incubation of gastric mucosae were used. We found that H. pylori infection destroyed the mitochondria of parietal cells and reduced DA content in the gastric mucosa at 10 weeks after infection. Moreover, gastrin-positive cell numbers and serum gastrin levels were increased. D1R, but not D2R, was observed in G cells. DA promoted gastric gastrin secretion. Interestingly, both D1- and D2-like agonists mimicked the effect of DA on the gastrin secretion, which was antagonized by their antagonists. Blocking D2R with domperidone or knocking out D2R resulted in decreased gastrin-positive cell numbers and gastrin levels but increased SOM levels at 10 weeks after H. pylori infection. Our findings highlight the key regulatory effect of D2R on gastrin secretion and elucidate the role of domperidone in reducing the elevated gastrin level associated with H. pylori infection.

Most tumors of the digestive system, including esophageal, gastric, liver and colorectal cancer, are malignant tumors that are associated with rates of high morbidity and mortality. The lack of effective methods for early diagnosis is an important cause of poor prognosis for these malignancies. Circular RNAs (circRNAs) belong to a family of endogenous, covalently closed non-coding RNAs that are characterized as having no 5 ' cap structures or 3 ' poly-A tails. Shortly following discovery, circRNAs were considered to be a product of mis-splicing and have no significant biological function. However, in recent years, accumulating evidence is demonstrating that they serve key roles in tumorigenesis and have the potential to serve as diagnostic markers. The present article summarizes the biogenesis and function of circRNAs and reviews their role in seven common types of tumor of the digestive system whilst exploring their potential as tumor markers and the significant roles they can serve in the digestive system, in addition to providing a referencing point for future studies of digestive system malignancies.

Gastric cancer (GC) is one of the most common cancer types and the fourth leading cause of cancer-related mortality among all malignant tumors worldwide. Due to insidious onset and lack of reliable early diagnostic markers, most GC patients are at an advanced stage at the time of diagnosis. Annexin is an evolutionally-conserved Ca2+-dependent phospholipid-binding protein superfamily, including five members (A, B, C, D, and E). Annexins in the cells of vertebrates comprised the annexin A family, consisting of 12 members in humans. The biological functions of annexin A are Ca2+-signal transduction, vesicle transport, cell proliferation, cell division, cell apoptosis, signal transduction, anti-inflammatory, proangiogenesis, and anticoagulation, most of which overlap with the basic characteristics of tumors. Accumulating evidence indicated that members of the annexin A family are correlated with tumorigenesis and chemoresistance and can be used as potential tumor prognostic factors and targets for biological therapy. Thus, the current review focused on the role and relative mechanisms of the annexin A family in GC.

Altering energy metabolism to meet the uncontrolled proliferation and metastasis has emerged as one of the most significant hallmarks in tumors. However, the detailed molecular mechanisms and regulatory actions underlying have not been fully elucidated. As a family of NAD+ dependent protein modifying enzymes, sirtuins (SIRT1-SIRT7) have multiple catalytic functions such as deacetylase, desuccinylase, demalonylase, demyristoylase, depalmitoylase, and/or mono-ADP-ribosyltransferase. They play important roles in regulating cell metabolism, especially in glucose and lipid metabolism, thereby exerting complex functions in either increasing or decreasing malignant characteristics in tumors. This review highlights the major function and its mechanisms of sirtuins in cellular metabolic reprogramming, such as glucose metabolism including aerobic glycolysis (the Warburg effect), oxidative phosphorylation (OXPHOS)/tricarboxylic acid (TCA) cycle and glutamine metabolism; lipometabolism including fatty acid metabolism, cholesterol metabolism, ketone body metabolism and acetate metabolism; as well as leucine metabolism and the urea cycle in tumorigenesis and cancer development.

Outer inflammatory protein (OipA) is an important virulence factor ofHelicobacter pylori(H. pylori), but the correlation betweenoipAcopy number and its virulence remains unknown. The study was designed to investigate whether the duplicateoipAgene loci showed more virulent than oneoipAgene in vitro.H. pyloristrain CCS9803 (China Chongqing Strain 9803) that carries duplicateoipAloci was used to construct one or twooipAknockout mutant strain, which was further verified by qPCR and western blot. Gastric epithelial cells AGS and GES-1 were infected with wild-type (WT) oroipAmutants for 6 or 24 h. The expression levels of IL-8, bacterial adhesion, cell apoptosis and cell cycle were performed to analyze the function ofoipA. The WT andoipAmutant strains induce significantly higher mRNA and protein levels of IL-8 than the uninfected group (P < 0.05), but onlyoipA2 mutants induced significantly decreased expression levels than the WT-infected group (P < 0.05). Adherence to gastric cells was significantly decreased by inactivated twooipAloci (P < 0.05). The WT strain caused a significant rising proportion of early apoptosis cell, which had dropped after duplicateoipAgenes were both knockout (P < 0.05). WT andoipA1 mutants failed to affect cell cycle; however, theoipA2 mutants increased M phase and reduced S phase when compared to the uninfected group. In conclusion, our study demonstrated thatoipAimpacts IL-8 expression, adherence, cell apoptosis and cell cycle of gastric cells independent of its gene copy number.

Background: Exosomes play an important role in transferring information among different cell types, as they transport materials from the cell membrane to the cytoplasm. They are involved not only in normal physiological functions, but also in the occurrence and development of a variety of diseases. Cancer is a major health problem affecting humans. Currently, exosomes are considered novel stars in tumor therapy.Objective: To present a review focusing on the role of exosomes in tumorigenesis and development and the possibility of treating tumors with exosome-targeted therapies or using exosomes as carriers.Methods: We reviewed literature related to the biological origin and function of exosomes and exosome-tumor relationship.Results: Exosomes are closely related to tumor immunity, angiogenesis, pre-metastasis microenvironment, chemoresistance, energy metabolism, etc. Tumor therapy involving the targeting of exosomes involves block the generation, secretion, uptake of exosomes, and elimination of circulating exosomes, and develop antitumor vaccines. Exosome as delivery vehicles can be loaded with chemotherapeutic drugs, therapeutic genes, and other therapeutic drugs to target cells. Prospects and challenges of exosome-based tumor therapy are also discussed.Conclusion: Exosomes are involved in multiple processes during tumor development and should be further studied as novel targets for cancer therapy.

NUSAP1, which is a microtubule-associated protein involved in mitosis, plays essential roles in diverse biological processes, especially in cancer biology. In this study, NUSAP1 was found to be overexpressed in GBM tissues in a grade-dependent manner compared with normal brain tissues. NUSAP1 was also highly expressed in GBM patients, dead patients, and GBM cells. In addition, NUSAP1 was found to participate in cell proliferation, apoptosis, and DNA damage in GBM cells. Ataxia telangiectasia and Rad3-related protein (ATR) are a primary sensor of DNA damage, and ATR is also a promising target in cancer therapy. Here, we found that NUSAP1 positively regulated the expression of ATR. Mechanistically, NUSAP1 suppressed the ubiquitin-dependent proteolysis of ATR. The SAP (SAF-A/B, Acinus, and PIAS) domain is a common motif of many SUMO (small ubiquitin-like modifier) E3 ligases, and this domain is involved in substrate recognition and ligase activity. This study further demonstrated that the SAP domain of NUSAP1 promoted the sumoylation of ATR, and thereby antagonized the ubiquitination of ATR. These results suggest that NUSAP1 stabilizes ATR by sumoylation. Moreover, NUSAP1 potentiated chemotherapeutic resistance to temozolomide (TMZ) and doxorubicin (DOX) through its SAP domain. Overall, this study indicates that NUSAP1 is a promising therapeutic target in GBM.

The lack of new drugs and resistance to existing drugs are serious problems in gastric cancer(GC) treatment. The research found polyphenols possess anti-Helicobacter pylori(Hp) and antitumor activities and may be used in the research and development of drugs for cancer prevention and treatment. However, polyphenols are affected by their chemical structures and physical properties, which leads to relatively low bioavailability and bioactivity in vivo. The intestinal flora can improve the absorption, utilization, and biological activity of polyphenols, whereas polyphenol compounds can increase the richness of the intestinal flora, reduce the activity of carcinogenic bacteria, stabilize the proportion of core flora, and maintain homeostasis of the intestinal microenvironment. Our review summarizes the gastrointestinal flora-mediated mechanisms of polyphenol against GC.

Objective This meta-analysis aims to explore the diagnostic value and accuracy of circulating lncRNAs as biomarkers of digestive system tumors. Methods PubMed, Embase, Cochrane Library, and Web of science were searched for relevant articles that were published before April 2019, and a meta-analysis was conducted. Results 52 studies with 63 lncRNAs were discussed in the meta-analysis. The pooled sensitivity and specificity of diagnosis were 0.80 (95% CI: 0.79-0.81) and 0.76 (95% CI: 0.75-0.77), respectively. The pooled DOR (the diagnostic odds ratio) was 15.63 (95% CI: 12.77-19.12), and the overall AUC (the area under the curve) was 0.87. Besides, subgroup analyzes showed that the DOR and AUC of large sample sizes (>80), multiple lncRNAs, serum-based lncRNAs, and downregulation group were superior to those of small sample sizes (<= 80), single lncRNA, plasma-based lncRNAs, and upregulation group, respectively. The current data also highlight that the diagnostic accuracy of circulating lncRNAs in the case of colorectal cancer was higher than gastric cancer, hepatocellular carcinoma, esophageal carcinoma, and pancreatic cancer. And there is no difference in the perspective of geographical regions. Conclusion The circulating lncRNAs have high diagnostic value and accuracy in digestive system cancers and may serve as potential biomarkers.