CircUGGT2 downregulation by METTL14-dependent m6A modification suppresses gastric cancer progression and cisplatin resistance through interaction with miR-186-3p/MAP3K9 axis.

Chemoresistance is a major therapeutic challenge in advanced gastric cancer (GC). N6-methyladenosine (m6A) RNA modification has been shown to play fundamental roles in cancer progression. However, the underlying mechanisms by which m6A modification of circRNAs contributes to GC and chemoresistance remain unknown. We found that hsa_circ_0030632 (circUGGT2) was a predominant m6A target of METTL14, and METTL14 knockdown (KD) reduced circUGGT2 m6A levels but increased its mRNA levels. The expression of circUGGT2 was markedly increased in cisplatin (DDP)-resistant GC cells. CircUGGT2 KD impaired cell growth, metastasis and DDP-resistance in vitro and in vivo, but circUGGT2 overexpression prompted these effects. Furthermore, circUGGT2 was validated to sponge miR-186-3p and upregulate MAP3K9 and could abolish METTL14-caused miR-186-3p upregulation and MAP3K9 downregulation in GC cells. circUGGT2 negatively correlated with miR-186-3p expression and harbored a poor prognosis in patients with GC. Our findings unveil that METTL14-dependent m6A modification of circUGGT2 inhibits GC progression and DDP resistance by regulating miR-186-3p/MAP3K9 axis.

METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis.

BACKGROUND: N6-methyladenosine (m6A) RNA methylation and circular RNAs (circRNAs) have been shown to act vital roles in multiple malignancies including gastric cancer (GC). However, there is little knowledge about how m6A modification of circRNAs contributes to GC progression. METHODS: The association of METTL14 expression with the clinicopathological characteristics and prognosis in patients with GC was assessed by Western blot, Immunohistochemistry and public datasets. In vitro and vivo function experiments were conducted to investigate the role of METTL14 in GC. Furthermore, m6A-circRNA epitranscriptomic microarray was utilized to identify METTL14-mediated m6A modification of circRNAs, which were validated by methylated RNA immunoprecipitation (Me-RIP), RT-qPCR and rescue experiments in GC cells. The sponge of circORC5 with miR-30c-2-3p was confirmed by luciferase gene report and RNA immunoprecipitation assays. The expression, localization and prognosis of circORC5 in GC were evaluated by fluorescence in situ hybridization. The effects of METTL14 and (or) circORC5 on miR-30c-2-3p-mediated AKT1S1 and EIF4B were estimated by RT-qPCR and Western blot analyses. RESULTS: We found that METTL14 was downregulated in GC tissue samples and its low expression acted as a prognostic factor of poor survival in patients with GC. Ectopic expression of METTL14 markedly repressed growth and invasion of GC cells in vitro and in vivo, whereas knockdown of METTL14 harbored the opposite effects. Mechanically, m6A-circRNA epitranscriptomic microarray and Me-RIP identified circORC5 as the downstream target of METTL14. Silencing of METTL14 reduced the m6A level of circORC5, but increased circORC5 expression. Moreover, circORC5 could sponge miR-30c-2-3p, and reverse METTL14-caused upregulation of miR-30c-2-3p and downregulation of AKT1S1 and EIF4B. In addition, circORC5 possessed a negative correlation with miR-30c-2-3p and indicated a poor survival in GC. CONCLUSION: Our findings demonstrate that METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis.

Alterations in the saliva microbiome in patients with gastritis and small bowel inflammation.

The oral microbiome is an important part of the human microbiome. Accumulating data have shown that oral microbiome alterations are closely related to multiple human diseases. However, salivary microbiota distributions remain unclear in patients with gastritis and small bowel inflammation. Magnetically guided capsule endoscopy (MGCE) is a noninvasive diagnostic tool for patients with gastritis and small bowel inflammation. Herein, we analysed the alterations in saliva microbiota in the normal, small intestinal inflammation and chronic gastritis groups through 16S rRNA gene amplicon sequencing. We found that the abundance of Lactobacillaceae was dramatically higher in chronic gastritis group than healthy individuals (p = 0.001). The levels of Porphyromonas and Faecalibaculum in gastritis samples were increased (p = 0.028; p = 0.006), and the enrichments of Faecalibaculum and Kosakonia in small intestine inflammation samples were elevated (p < 0.001; p = 0.002) compared to those in normal individuals. Our findings clarify the saliva microbiota components and their importance of specific bacteria in gastritis and small bowel inflammation.

Mucosal microbiome dysbiosis associated with duodenum bulb inflammation.

BACKGROUND: There is high morbidity in clinical patients with duodenum bulb inflammation. Mucosa-associated microbiota, which are closely related to inflammatory processes, may have a pathogenic role, but the duodenum bulb microbial signature is poorly studied. OBJECTIVE: This study aimed to characterize microbial changes associated with duodenum bulb inflammation. METHODS: Mucosal biopsy is commonly used to assess microbial communities associated with the intestinal mucosa. Sixteen patients (8 with duodenum bulb inflammation and 8 controls) underwent gastroscopy, and duodenal bulb biopsies were obtained. Diagnoses were based on both endoscopic and histological findings. To determine microbiota composition and diversity, 454 pyrosequencing of bacterial 16S rRNA and multiple bioinformatics analyses were performed. OTU-level alpha diversity indices, such as the Chao1 richness estimator, abundance-based coverage estimator (ACE) metric, Shannon diversity index, and Simpson index, were calculated using the OTU table in QIIME. RESULTS: More OTUs were identified in the normal samples (781) than in the inflammatory samples (553). Metastats analysis identified 19 phyla and 97 genera that were significantly different between the two groups, and the beta diversity was significantly different between the two groups (unweighted UniFrac: P = 0.001; weighted UniFrac: P = 0.001). For all individuals, composition analyses showed that the most abundant phyla in the duodenal bulb samples were Fusobacteria, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. The phylogenetic diversity of the microbiota in the duodenal bulbs of healthy volunteers was higher than that in volunteers with inflammation. Dominant microbes differed between the DN samples and DI samples. The most frequently represented genera in the DN samples were Cetobacterium, Aeromonadaceae, and Clostridium (accounting for 58.4%, 8.5%, and 4.8% of the total, respectively), and the dominant genera in the DI samples were Cetobacterium, Cupriavidus, and Helicobacter (accounting for 43.6%, 13.1%, 4.5% of the total, respectively). Significant differences in the microbiota were observed between those exhibiting an inflammatory state and the controls. CONCLUSIONS: These results confirm that the dominant species in duodenum bulbs differ between healthy subjects and patients with inflammation and that mucosal microbiome dysbiosis is involved in the development of duodenum bulb inflammation.

Novel insights into the interplay between m6A modification and noncoding RNAs in cancer.

N6-methyladenosine (m6A) is one of the most common RNA modifications in eukaryotes, mainly in messenger RNA (mRNA). Increasing evidence shows that m6A methylation modification acts an essential role in various physiological and pathological bioprocesses. Noncoding RNAs (ncRNAs), including miRNAs, lncRNAs and circRNAs, are known to participate in regulating cell differentiation, angiogenesis, immune response, inflammatory response and carcinogenesis. m6A regulators, such as METTL3, ALKBH5 and IGF2BP1 have been reported to execute a m6A-dependent modification of ncRNAs involved in carcinogenesis. Meanwhile, ncRNAs can target or modulate m6A regulators to influence cancer development. In this review, we provide an insight into the interplay between m6A modification and ncRNAs in cancer.

Mild changes in the mucosal microbiome during terminal ileum inflammation.

Patients with inflammation in the terminal ileum have high morbidity. In genetically susceptible hosts, chronic intestinal inflammation targeting the resident intestinal microbiota develops, but the microbial signature of the terminal ileum is poorly studied. To improve understanding of the mechanisms underlying the high prevalence of terminal ileum inflammation, we used 16S rRNA sequencing to analyse the mucosa-associated microbiota of the terminal ileum under intestinal homeostasis and inflammation conditions. Mucosal biopsy is the most commonly used sampling technique for assessing microbial communities associated with the intestinal mucosa. Thirty patients (15 with terminal ileum inflammation and 15 controls) underwent colonoscopy and biopsies were taken from the terminal ileum. Diagnosis depended on a combination of endoscopic and histological factors. To determine the composition and diversity of the microbiota, the 16S rRNA was analysed, and a variety of bioinformatics analyses were performed. Among the patients, composition analysis showed that the most abundant phyla identified in the terminal ileum samples were Fusobacteria, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. At the phylum level, the relative proportion of Bacteroidetes was lower in patients with inflammation than in control patients. In addition, there was an increase in the abundance of the phyla Proteobacteria and Lentisphaerae in patients with inflammation. The abundances of the dominant microbes in the terminal ileum were not significantly different between patients in an inflammatory state and controls. These results confirm that partial dysbiosis of the intestinal mucosa-associated microbiota composition is associated with terminal ileum inflammation.

The role of m6A RNA methylation in human cancer.

N6-methyladenosine (m6A) is identified as the most common, abundant and conserved internal transcriptional modification, especially within eukaryotic messenger RNAs (mRNAs). M6A modification is installed by the m6A methyltransferases (METTL3/14, WTAP, RBM15/15B and KIAA1429, termed as "writers"), reverted by the demethylases (FTO and ALKBH5, termed as "erasers") and recognized by m6A binding proteins (YTHDF1/2/3, IGF2BP1 and HNRNPA2B1, termed as "readers"). Acumulating evidence shows that, m6A RNA methylation has an outsize effect on RNA production/metabolism and participates in the pathogenesis of multiple diseases including cancers. Until now, the molecular mechanisms underlying m6A RNA methylation in various tumors have not been comprehensively clarified. In this review, we mainly summarize the recent advances in biological function of m6A modifications in human cancer and discuss the potential therapeutic strategies.

Sanguinarine inhibits growth and invasion of gastric cancer cells via regulation of the DUSP4/ERK pathway.

Sanguinarine, a bioactive benzophenanthridine alkaloid extracted from plants of the Papaveraceae family, has shown antitumour effects in multiple cancer cells. But the therapeutic effects and regulatory mechanisms of sanguinatine in gastric cancer (GC) remain elusive. This study was aimed to investigate the correlation of dual-specificity phosphatase 4 (DUSP4) expression with clinicopathologic features and overall survival in patients with GC and explore the effects of sanguinarine on tumour growth and invasion in GC cells (SGC-7901 and HGC-27) and underlying molecular mechanisms. Immunohistochemical analysis showed that decreased DUSP4 expression was associated with the sex, tumour size, depth of invasion and distant metastasis in patients with GC. Functional experiments including CCK-8, Transwell and flow cytometry analysis indicated that sanguinarine or DUSP4 overexpression inhibited GC cell viability and invasive potential, and induced cell apoptosis and cycle arrest in S phase, but DUSP4 knockdown attenuated the antitumour activity of sanguinarine. Further observation demonstrated that sanguinarine up-regulated the expression of DUSP4 and Bcl-2-associated X protein (Bax), but down-regulated phosphorylated extracellular signal-regulated kinase (p-ERK), proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP-2) and B-cell lymphoma 2 (Bcl-2) expression. Taken together, our findings indicate that sanguinarine inhibits growth and invasion of GC cells through regulation of the DUSP4/ERK pathway, suggesting that sanguinarine may have potential for use in GC treatment.

Helicobacter Pylori-Enhanced hnRNPA2B1 Coordinates with PABPC1 to Promote Non-m6A Translation and Gastric Cancer Progression.

Helicobacter pylori (H. pylori) infection is the primary risk factor for the pathogenesis of gastric cancer (GC). N6-methyladenosine (m6A) plays pivotal roles in mRNA metabolism and hnRNPA2B1 as an m6A reader is shown to exert m6A-dependent mRNA stabilization in cancer. This study aims to explore the role of hnRNPA2B1 in H. pylori-associated GC and its novel molecular mechanism. Multiple datasets and tissue microarray are utilized for assessing hnRNPA2B1 expression in response to H. pylori infection and its clinical prognosis in patients with GC. The roles of hnRNPA2B1 are investigated through a variety of techniques including glucose metabolism analysis, m6A-epitranscriptomic microarray, Ribo-seq, polysome profiling, RIP-seq. In addition, hnRNPA2B1 interaction with poly(A) binding protein cytoplasmic 1 (PABPC1) is validated using mass spectrometry and co-IP. These results show that hnRNPA2B1 is upregulated in GC and correlated with poor prognosis. H. pylori infection induces hnRNPA2B1 upregulation through recruiting NF-κB to its promoter. Intriguingly, cytoplasm-anchored hnRNPA2B1 coordinated PABPC1 to stabilize its relationship with cap-binding eIF4F complex, which facilitated the translation of CIP2A, DLAT and GPX1 independent of m6A modification. In summary, hnRNPA2B1 facilitates the non-m6A translation of epigenetic mRNAs in GC progression by interacting with PABPC1-eIF4F complex and predicts poor prognosis for patients with GC.

Detachable string magnetically controlled capsule endoscopy for the noninvasive diagnosis of esophageal diseases: A prospective, blind clinical study.

BACKGROUND: Traditional esophagogastroduodenoscopy (EGD), an invasive examination method, can cause discomfort and pain in patients. In contrast, magnetically controlled capsule endoscopy (MCE), a noninvasive method, is being applied for the detection of stomach and small intestinal diseases, but its application in treating esophageal diseases is not widespread. AIM: To evaluate the safety and efficacy of detachable string MCE (ds-MCE) for the diagnosis of esophageal diseases. METHODS: Fifty patients who had been diagnosed with esophageal diseases were prospectively recruited for this clinical study and underwent ds-MCE and conventional EGD. The primary endpoints included the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of ds-MCE for patients with esophageal diseases. The secondary endpoints consisted of visualizing the esophageal and dentate lines, as well as the subjects' tolerance of the procedure. RESULTS: Using EGD as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of ds-MCE for esophageal disease detection were 85.71%, 86.21%, 81.82%, 89.29%, and 86%, respectively. ds-MCE was more comfortable and convenient than EGD was, with 80% of patients feeling that ds-MCE examination was very comfortable or comfortable and 50% of patients believing that detachable string v examination was very convenient. CONCLUSION: This study revealed that ds-MCE has the same diagnostic effects as traditional EGD for esophageal diseases and is more comfortable and convenient than EGD, providing a novel noninvasive method for treating esophageal diseases.

m6A reader YTHDF3 is associated with clinical prognosis, related RNA signatures and immunosuppression in gastric cancer.

BACKGROUND: YTHDF3 as a N6-methyladenosine (m6A) reader participates in the development and progression of multiple cancer types, however, the prognosis, molecular biology and immune infiltration of YTHDF3 in gastric cancer (GC) have not been investigated. METHODS: The YTHDF3 expression profile and clinicopathological parameters of stomach adenocarcinoma (STAD) were downloaded from TCGA. The online websites and databases such as GEPIA2, cBioPortal, UALCAN, ImmuCellAl, xCell, TISIDB, GSCA were utilized for analysis of the association of YTHDF3 with STAD, including clinical prognosis, WGCNA and LASSO Cox regression analysis. Further functional assays such as RT-qPCR, Western blot, immunohistochemistry (IHC), immunofluorescence (IF), CCK-8, colony formation, EdU and Transwell assays were performed to determine the role of YTHDF3 in GC. RESULTS: We found that YTHDF3 was upregulated in STAD tissue samples ascribed to its copy number amplification and associated with poor prognosis in patients with STAD. GO and KEGG analyses showed that YTHDF3-related differential genes were predominantly enriched in the proliferation, metabolism and immune signaling pathways. Knockdown of YTHDF3 repressed the growth and invasion of GC cells by inhibition of PI3K/AKT signaling. We then identified YTHDF3-related lncRNAs, miRNAs and mRNAs, and constructed their prognostic signatures in patients with STAD. Moreover, YTHDF3 associated with tumor immune infiltration such as CD8+ T cells, macrophages, Tregs, MHC molecules and chemokines, upregulated PD-L1 and CXCL1 and exerted a response to the immunotherapy in GC. CONCLUSIONS: YTHDF3 upregulation indicates poor prognosis and promotes GC cell growth and invasion by activating PI3K/AKT pathway and regulating immune microenvironment. The established YTHDF3-related signatures highlight the association of YTHDF3 with the clinical prognosis and immune cell infiltration in GC.

RNA interference mediated YAP gene silencing inhibits invasion and metastasis of human gastric cancer cell line SGC-7901.

BACKGROUND/AIMS: This study aimed to investigate the effects of yes-associated protein (YAP) silencing on invasion, migration, anchorage-independent growth and angiogenesis in the human gastric cancer cell line SGC-7901. METHODOLOGY: SGC-7901 cells were transfected with a shRNA lentivirus vector targeting YAP gene. After puromycin selection of stable YAP-silenced SGC-7901 cell lines, the expression of YAP mRNA and protein were detected using quantitative real-time PCR (qRT-PCR) and western blotting. A transwell invasion assay, wound healing assay and colony formation assay were used to analyze the invasion, migration and anchorage-independent growth effect of RNA interference (RNAi) on YAP expression. The angiogenic cytokines, vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2), were measured by qRT-PCR and western blotting. RESULTS: The results of the qRT-PCR and western blotting showed an obvious inhibition of YAP mRNA and protein expression in the YAP-shRNA group. Moreover, the inhibition of YAP expression clearly impeded SGC-7901 cell migration, invasion and anchorage-independent growth. Furthermore, VEGF and FGF-2 were also downregulated. CONCLUSIONS: YAP gene targeting by RNAi can inhibit the migration, invasion, anchorage-independent growth and angiogenesis ability of SGC-7901 cells. YAP may be a potential target for the treatment of human gastric cancer.

A breakdown of the Hippo pathway in gastric cancer.

BACKGROUND/AIMS: The Hippo pathway is a newly discovered signaling pathway. In mammals, the Hippo pathway was reported to be a tumor-suppressor signaling that inhibited cell proliferation and promoted cell apoptosis. Inactivation of the Hippo pathway resulted in massive cell growth, enlargement in organ size and eventually cancer formation. The aim of this study was to investigate the expression of core component proteins of the Hippo pathway, Mst1/2,S Sav1 and Lats1, in normal gastric mucosa, intestinal metaplasia and gastric cancer, and to explore the role of the Hippo pathway in gastric cancer. METHODOLOGY: Two-step immunohistochemical staining was used to detect the expression of Mst1/2, Sav1 and Lats1 in 46 cases of normal gastric mucosa, 37 cases of intestinal metaplasia and 78 cases of gastric cancer. RESULTS: The expression of Mst1/2 and Lats1 was down-regulated in gastric cancer compared with that in normal gastric epithelium and adenoma. The Sav1 expression showed an increased trend from normal mucosa through intestinal metaplasia to gastric cancer, though there was no statistically significant difference. The expression of Sav1 and Lats1 in gastric cancer with lymph node metastasis was significantly lower than that without lymph node metastasis. CONCLUSIONS: A breakdown of the Hippo pathway may play a role in tumorigenesis and metastasis of gastric cancer.

Dihydroartemisinin inhibits the tumorigenesis and invasion of gastric cancer by regulating STAT1/KDR/MMP9 and P53/BCL2L1/CASP3/7 pathways.

Dihydroartemisinin (DHA), an effective antimalarial drug, has been widely investigated as an anti-tumor agent. Although previous studies have indicated the potential therapeutic effects of DHA on multiple malignancies, its detailed molecular mechanisms in gastric cancer (GC) are still undocumented. In the present study, we applied network pharmacology and bioinformatics (gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses) to obtain the collective targets of DHA and GC and analyzed their involvement in constructing a protein-protein interaction (PPI) network. The top 10% hub targets in this network were identified, and TCGA database was utilized for the single gene analysis of their correlation with the prognosis of GC. CCK8, EdU, Transwell, and flow cytometry analyses were conducted, and subcutaneous xenograft tumor models were constructed to assess the effects of DHA on the tumorigenesis and invasion of GC. Furthermore, the targets of DHA were verified by molecular docking, quantitative real-time PCR (qPCR) and western blot analyses in GC cells. The results indicated that the common targets of DHA and GC were enriched in multiple cancer-related pathways including KDR, STAT1 and apoptosis signaling pathways, where the core genes included KDR, MMP9, STAT1, TP53, CASP3/7 and BCL2L1. The lowered expression of KDR and increased expression of TP53 and CASP7 harbored a favorable survival for patients with GC patients. CASP7 showed a positive correlation with CASP3 but a negative correlation with KDR and could be regarded as an independent protective factor for overall survival in GC. Moreover, DHA treatment induced cell apoptosis and suppressed the cell proliferation, DNA synthesis, cycle progression and invasive capabilities both in vitro and in vivo. DHA also upregulated p53, CASP3, and cleaved-CASP3 and downregulated BCL2L1, MMP9, KDR, p-KDR, STAT1 and p-STAT1 in GC cell lines. In conclusion, DHA could suppress the tumorigenesis and invasion of GC by regulating STAT1/KDR/MMP9 and p53/BCL2L1/CASP3/7 pathways. Our findings might provide a novel approach for the treatment of GC.

Dihydroartemisinin Suppresses the Tumorigenesis and Cycle Progression of Colorectal Cancer by Targeting CDK1/CCNB1/PLK1 Signaling.

Dihydroartemisinin (DHA), a well-known antimalarial drug, has been widely investigated for its antitumor effects in multiple malignancies. However, its effects and regulatory mechanisms in colorectal cancer (CRC) are still unproved. In this study, in vitro experiments including CCK8, EdU, Transwell, and flow cytometry analyses and an in vivo tumorigenesis model were conducted to assess the effects of DHA on the bio-behaviors of CRC cells. Additionally, RNA-seq combined with gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses was used to obtain the targets of DHA, and these were verified by molecular docking, qRT-PCR, and Western blotting. As a result, we found that DHA significantly suppressed the proliferation, DNA synthesis, and invasive capabilities and induced cell apoptosis and cell cycle arrest in HCT116, DLD1, and RKO cells in vitro and in vivo. Further analyses indicated that the targets of DHA were predominantly enriched in cell cycle-associated pathways, including CDK1, CCNB1, and PLK1; and DHA could bind with the CDK1/CCNB1 complex and inhibit the activation of CDK1/CCNB1/PLK1 signaling. Moreover, cucurbitacin E, a specific inhibitor of the CDK1/CCNB1 axis, enhanced the inhibitory effects of DHA on DNA synthesis and colony formation in HCT116 and DLD1 cells. In short, DHA could suppress the tumorigenesis and cycle progression of CRC cells by targeting CDK1/CCNB1/PLK1 signaling.

The m6A Reader YTHDF1 Facilitates the Tumorigenesis and Metastasis of Gastric Cancer via USP14 Translation in an m6A-Dependent Manner.

OBJECTIVES: N6-methyladenosine (m6A) RNA methylation is implicated in the progression of multiple cancers via influencing mRNA modification. YTHDF1 can act as an oncogene in gastric cancer (GC), while the biological mechanisms via which YTHDF1 regulates gastric tumorigenesis through m6A modification remain largely unknown. METHODS: GEO and TCGA cohorts were analyzed for differentially expressed m6A modification components in GC clinical specimens and their association with clinical prognosis. Transwell and flow cytometry assays as well as subcutaneous xenograft and lung metastasis models were used to evaluate the phenotype of YTHDF1 in GC. Intersection of RNA/MeRIP-seq, luciferase assay, RIP-PCR, RNA pull-down and MeRIP-PCR was used to identify YTHDF1- modified USP14 and its m6A levels in GC cells. RESULTS: High-expressed YTHDF1 was found in GC tissues and was related to poor prognosis, acting as an independent prognostic factor of poor survival in GC patients. YTHDF1 deficiency inhibited cell proliferation and invasion (in vitro), and gastric tumorigenesis and lung metastasis (in vivo) and also induced cell apoptosis. Intersection assays revealed that YTHDF1 promoted USP14 protein translation in an m6A-dependent manner. USP14 upregulation was positively correlated with YTHDF1 expression and indicated a poor prognosis in GC. CONCLUSION: Our data suggested that m6A reader YTHDF1 facilitated tumorigenesis and metastasis of GC by promoting USP14 protein translation in an m6A-dependent manner and might provide a potential target for GC treatment.

CircPTK2 inhibits the tumorigenesis and metastasis of gastric cancer by sponging miR-134-5p and activating CELF2/PTEN signaling.

BACKGROUND: CircRNAs are a new subset of noncoding RNAs formed by covalent closed loops and play crucial roles in the regulation of cancer gene expression. However, the roles and underlying mechanisms of circRNAs in gastric cancer (GC) remain indistinct. This study aimed to explore the role and mechanism of hsa_circ_0006421 (circPTK2) in GC. METHODS: The differential expression of circRNAs between GC tissues and adjacent normal tissues were identified by a circRNA expression profiling. Associations of circPTK2 or miR-134-5p expression with clinicopathological characteristics and prognosis of GC patients were analyzed by chi-square of Fisher's exact tests and Kaplan-Meier analysis. CCK8, colony formation, EdU assays and animal models were performed to assess the effects of circPTK2 on proliferation and invasion of GC cells. CircPTK2-specific probes were used to purify the RNA pulled down from the circPTK2, and enrichment of circPTK2 and miR-134-5p was detected by qRT-PCR. The effects of circPTK2 on miR-134-5p expression and CELF2/PTEN signaling were examined by qRT-PCR and Western blotting analysis. RESULTS: Low expression of circPTK2 and high expression of miR-134-5p were related to the poor survival, and high expression of miR-134-5p was related to the tumor recurrence in GC patients. Overexpressing circPTK2 suppressed the proliferation, colony formation, DNA synthesis and cell invasion as well as xenograft tumor growth and lung metastasis in vitro and in vivo, whereas silencing circPTK2 had the opposite effects. Moreover, circPTK2 was negatively correlated and co-localized with miR-134-5p in the cytoplasm of GC tissue cells. circPTK2 bound to and sponged miR-134-5p in GC cells, and miR-134-5p facilitated cell growth and invasion but attenuated circPTK2 induced tumor suppressive effects and CELF2/PTEN signaling activation in GC cells. CONCLUSIONS: circPTK2 functions as a tumor suppressor in GC by sponging miR-134-5p and activating the CELF2/PTEN axis.

The Detective Value of Magnetically Controlled Robotic Capsule Endoscopy in Patients With Suspected Small Intestinal Disease.

Objective: To explore the detective value of magnetically controlled robotic capsule endoscopy (MCRCE) in patients with suspected small intestinal disease. Patients and Methods: In total, 1,802 patients with suspected small intestinal disease and negative gastroenteroscopy from Shanghai Jiao Tong University Affiliated Sixth People's Hospital were examined with MCRCE, and the data were collected for further analysis. Results: Among the 1,802 patients who were examined with MCRCE, 974 were diagnosed with small intestinal disease, reaching a positive detection rate of 54.1%. The five most common conditions that were detected include non-specific enteritis in 722 cases (40.1%), small intestinal ulcers in 87 cases (4.8%), abnormal small bowel evacuation in 45 cases (2.5%), small intestinal bleeding in 33 cases (1.8%), and small intestinal yellow spots in 31 cases (1.7%). The running time of the capsules in the small intestine ranged from 85-437 min, with an average of 210.24 ± 89.08 min. No complications, such as intestinal obstruction or capsule retention, were observed in all patients. Conclusion: MCRCE is a safe and non-invasive endoscopic examination with a highly accurate detection rate for small intestinal diseases.

[Effects of oxymatrine injection combined with low-dose paclitaxel on mRNA and protein expressions of vascular endothelial growth factor and CXC chemokine receptor 4 in human gastric carcinoma SGC-7901 cells].

OBJECTIVE: To investigate the effects of oxymatrine injection (OI) combined with low-dose paclitaxel on expressions of mRNAs and proteins of vascular endothelial growth factor (VEGF) and CXC chemokine receptor 4 (CXCR4) in human gastric carcinoma SGC-7901 cells. METHODS: Methyl thiazolyl tetrazolium assay was used to examine the effects of OI combined with low-dose paclitaxel on proliferation of SGC-7901 cells. Real-time reverse transcription-polymerase chain reaction, immunofluorescence and enzyme-linked immunosorbent assay were employed to measure the expressions of VEGF and CXCR4 mRNAs and proteins in gastric carcinoma SGC-7901 cells respectively. RESULTS: Except that 20 µg/mL paclitaxel had no influence on expression of VEGF mRNA in SGC-7901 cells (P>0.05), 40 µg/mL OI or low-dose paclitaxel (20 µg/mL) inhibited the proliferation of SGC-7901 cells and reduced the expressions of VEGF and CXCR4 mRNAs and proteins in SGC-7901 cells (P<0.01). The expressions of VEGF and CXCR4 mRNAs and proteins in the OI plus low-dose paclitaxel group were markedly lower than those in the low-dose paclitaxel group (P<0.01). CONCLUSION: OI combined with low-dose paclitaxel can inhibit VEGF and CXCR4 of gastric carcinoma SGC-7901 cells markedly, which may be one of its mechanisms of anti-angiogenic ability.

Dihydroartemisinin prevents dextran sodium sulphate-induced colitisthrough inhibition of the activation of NLRP3 inflammasome and p38 MAPK signaling.

Dihydroartemisinin (DHA), a sesquiterpene lactone derived from artemisinin, has been reported to possess anti-inflammation and anti-cancer activities. But its underlying protective mechanisms on dextran sodium sulphate (DSS)-induced colitis remain rarely reported. We applied a network pharmacology approach to predict the collective targets of DHA and acute colitis. GO and KEGG analyses were performed to investigate the enriched biological functions and signaling pathways of the collective targets. Furthermore, a DSS-induced colitis model was established to observe the protective effects of DHA. 83 common targets of DHA and acute colitis were identified and predominantly involved in several inflammation-related signaling pathways in colitis such as NOD-like receptor and MAPK signaling pathways. Additionally, DHA in vivo improved the clinical symptoms, reduced the production of pro-inflammatory factors IL-1ß, IL-6 and TNF-α, and suppressed the formation of NLRP3 inflammasome. Moreover, DHA inhibited the phosphorylation of NF-κB p65 and p38 MAPK, but upregulated PPARγ and Ki-67 levels compared to the DSS group. Additionally, we found that DHA suppressed p38 activator-induced pro-inflammatory response, and p38 inhibitor attenuated the clinical symptoms and reduced the expression levels of pro-inflammatory mediators and NLRP3 while up-regulated the expression levels of PPARγ and Ki-67. Molecular docking analysis further verified the binding mode towards the DHA and p38 MAPK. In conclusion, DHA could protect DSS-induced colitis via suppressing the activation of NLRP3 inflammasome and p38 MAPK signaling.