Background Gastric carcinoma (GC) is currently one of the most common malignant tumors of the digestive system, and gastric precancerous lesions play a vital role in studying the mechanism of GC. Multiple microRNAs (miRNAs) have been documented to be potential biomarkers to indicate progression of gastric precancerous lesions. In this study, we explained the anti-cancer effect of miR-365 in gastric precancerous lesions via regulation of the TLR4/IRF3/YAP/CDX2 axis. Methods miR-365, TLR4, CDX2 and IPF3 expression was determined in GC and atrophic gastritis tissues and cells. After transfection of shRNA and overexpression plasmids, in vitro experiments detected the alteration of cell viability, apoptosis and inflammatory factors. Bioinformatics analysis, Co-IP and dual luciferase reporter gene assay were conducted to evaluate the binding between miR-365 and TLR4 as well as IRF3 and YAP. Rat models were established to explore the effect of the miR-365 and TLR4 on gastric precancerous lesions. Results miR-365 was poorly expressed in GC and atrophic gastritis tissues and GC cell lines, while TLR4, CDX2 and IRF3 were overexpressed. Of note, miR-365 was indicated to target TLR4 and thereby suppressed cancer progression and increased hemoglobin content. Interestingly, silencing of TLR4 was accompanied by decreased IRF3 phosphorylation and reduced expression with less binding between CDX2 and IRF3. Downregulation of YAP resulted in declined CDX2 expression in cancer cells. Moreover, the inhibitory role of miR-365 was further confirmed in animal models. Conclusion Taken together, miR-365-mediated TLR4 inhibition reduces IRF3 phosphorylation and YAP-mediated CDX2 transcription to impede progression of gastric precancerous lesions.

FAT atypical cadherin 1 (FAT1) is a mutant gene frequently found in human cancers and mainly accumulates at the plasma membrane of cancer cells. Emerging evidence has implicated FAT1 in the progression of gastric cancer (GC). This study intended to identify a regulatory network related to FAT1 in GC development. Upregulated expression of FAT1 was confirmed in GC tissues, and silencing FAT1 was observed to result in suppression of GC cell oncogenic phenotypes. Mechanistic investigation results demonstrated that FAT1 upregulated AP‐1 expression by phosphorylating c‐JUN and c‐FOS, whereas LINC00857 elevated the expression of FAT1 by recruiting a transcription factor TFAP2C. Functional experiments further suggested that LINC00857 enhanced the malignant biological characteristics of GC cells through TFAP2C‐mediated promotion of FAT1. More importantly, LINC00857 silencing delayed the tumor growth and blocked epithelial–mesenchymal transition in tumor‐bearing mice, which was associated with downregulated expression of TFAP2C/FAT1. To conclude, LINC00857 plays an oncogenic role in GC through regulating the TFAP2C/FAT1/AP‐1 axis. Therefore, this study contributes to extended the understanding of gastric carcinogenesis and LINC00857 may serve as a therapeutic target for GC.

Gastric cancer (GC) as a serious global health problem is a threat to human longevity. Plasmacytoma variant translocation 1 (PVT1) participates in the formation and progression of various cancers, including GC. The aim of this study is to investigate the mechanism underlying the functions of PVT1 and explore a novel target for the diagnosis and treatment of GC. Analysis of the TCGA dataset using the R software identified that the lncRNA PVT1 was greatly upregulated in GC tissues. Twenty pairs of GC and adjacent normal tissues were acquired from patients with GC, and the expression of PVT1 was evaluated using RT-qPCR. Furthermore, PVT1 expression was knocked down in GC cells using siRNA, and the GC cells were divided into control, negative control (NC), and siRNA groups. Cell proliferation ability was analyzed using Cell Counting Kit-8 (CCK8) and colony formation assays, whereas cell migration and invasion ability were investigated through wound healing and Transwell assays. Moreover, Western blotting was used to analyze the expression of Yes-associated protein (YAP) and epithelial-to-mesenchymal transition (EMT) proteins. We also found that PVT1 and YAP expressions were upregulated in the GC tissues compared with those in the adjacent nontumor tissues. Knockdown of PVT1 was found to inhibit the proliferation, invasion, and migration and promote apoptosis of GC cells. Furthermore, knockdown of PVT1 downregulated YAP and promoted phosphorylation of YAP, suggesting that PVT1 exerts actions on GC cells by targeting YAP and inhibits cell apoptosis in vitro. The EMT process was also inhibited by the knockdown of PVT1. In summary, lncRNA PVT1 facilitated cell proliferation, invasion, and migration and suppressed cell apoptosis by targeting YAP. This study suggests that the expressions of PVT1 and YAP could be used for the early detection of GC and the occurrence and development of GC could be inhibited by interfering the interaction of PVT1 and YAP, which will provide new insights for the diagnosis, treatment, and prognosis of GC.

BACKGROUND Endoscopic submucosal dissection (ESD) has been advocated by digestive endoscopists because of its comparable therapeutic effect to surgery, reduced trauma, faster recovery, and fewer complications. However, ESD for lesions of the duodenum is more challenging than those occurring at other levels of the gastrointestinal tract due to the thin intestinal wall of the duodenum, narrow intestinal space, rich peripheral blood flow, proximity to vital organs, and high risks of critical adverse events including intraoperative and delayed bleeding and perforation. Because of the low prevalence of the disease and the high risks of severe adverse events, successful ESD for lesions of the duodenum has rarely been reported in recent years. AIM To investigate the efficacy and safety of ESD in the treatment of duodenal space-occupying lesions. METHODS Clinical data of 24 cases of duodenal lesions treated by ESD at the Digestive Endoscopy Center of the Affiliated Hospital of Qingdao University from January 2016 to December 2019 were retrospectively analyzed. RESULTS All of the 24 cases from 23 patients underwent ESD treatment for duodenal space-occupying lesions under general anesthesia, including 15 male and 8 female patients, with a mean age of 58.5 (32.0-74.0) years. There were 12 lesions (50%) in the duodenal bulb, 9 (37.5%) in the descending part, and 3 (12.5%) in the ball-descending junction. The mean diameter of the lesion was 12.75 (range, 11-22) mm. Thirteen lesions originated from the mucosa, of which 4 were low-grade intraepithelial neoplasia, 3 were hyperplastic polyps, 2 were chronic mucositis, 2 were adenomatous hyperplasia, 1 was high-grade intraepithelial neoplasia, and 1 was tubular adenoma. Eleven lesions were in the submucosa, including 5 neuroendocrine neoplasms, 2 cases of ectopic pancreas, 1 stromal tumor, 1 leiomyoma, 1 submucosal duodenal adenoma, and 1 case of submucosal lymph follicular hyperplasia. The intraoperative perforation rate was 20.8% (5/24), including 4 submucosal protuberant lesions and 1 depressed lesion. The mean length of hospital stay was 5.7 (range, 3-10) d, and the average follow-up time was 25.8 (range, 3.0–50.0) mo. No residual disease or recurrence was found in all patients, and no complications, such as infection and stenosis, were found during the follow-up period. CONCLUSION ESD is safe and effective in the treatment of duodenal lesions; however, the endoscopists should pay more attention to the preoperative preparation, intraoperative skills, and postoperative treatment.