Objectives Circular RNAs (circRNAs) are RNA transcripts that belong to non‐coding RNAs (ncRNAs), whose implication in human cancers has been recently demonstrated. However, the specific role of multiple circRNAs in breast cancer remains unidentified. Materials and methods Microarray analysis and bioinformatics analysis were applied to select circRNA and miRNA, respectively. The loop structure of circ‐TFF1 was confirmed using RNase R treatment, divergent primer PCR and Sanger sequencing. qRT‐PCR and Western blot were employed for gene expressions. In vitro and in vivo experiments were conducted to assess the function of circ‐TFF1 in biological processes in breast cancer cells. FISH and subcellular separation indicated circ‐TFF1 cellular distribution. Luciferase reporter and RIP assays and Pearson's correlation analysis were performed to evaluate relationships between genes. Results Circ‐TFF1 and TFF1 were both upregulated and positively associated with each other in breast cancer. Knockdown of circ‐TFF1 hindered breast cancer cell proliferation, migration, invasion and EMT in vitro and controlled tumour growth in vivo. Circ‐TFF1 acted as a ceRNA of TFF1 by sponging miR‐326, and its contribution to breast cancer progression was mediated by miR‐326/TFF1 axis. Conclusions Circ‐TFF1 is a facilitator in breast cancer relying on TFF1 by absorbing miR‐326, providing a novel promising target for BC treatment.

Background/Aims: Gastric neuroendocrine tumors (G-NETs) are uncommon neoplasms that can present with or without clinical symptoms. In this study, we evaluated the incidence, prognosis, and temporal trends of G-NETs. Methods: We analyzed all cases of G-NETs registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2014. Incidence was estimated by age and joinpoint analyses. Survival rates were calculated and survival trends over time were evaluated. Results: A total of 3740 eligible patients were enrolled in the study. G-NETs incidence increased from 0.31 per 1 000 000 patients in 1975 to 4.85 in 2014, with an annual percentage changes (APCs) of 8.9% (95% confidence interval [CI] = 7.7% to 10.21%, P < 0.001, t test (29) from 1975 to 2001 and 3.6% from 2002 to 2014 (95% CI= 2.3% to 4.9%, P < 0.001). For cases diagnosed between 1973 and 1982, five-year survival was 62.8% ± 7.0% (Standard error, SE) and increased to 86.7% ± 0.7% for cases diagnosed between 2003 and 2012 (P < 0.001). Years of diagnosis, gender, age at diagnosis, marital status, grade, tumor size, tumor stage, and surgery performed or not were the strongest predictors of worse survival in both univariate and multivariate analysis (P<0.05). Conclusion: G-NETs are uncommon neoplasms but the incidence is growing. Survival has improved in the past decades. Years of diagnosis, gender, age at diagnosis, marital status, grade, tumor size, tumor stage, and surgery status predict survival in patients with G-NETs.

The epidermal growth factor receptor (EGFR) activates downstream mTOR phosphorylation to promote the progression of many different tumor types, thus making it a prime therapeutic target. However, the role of DEP domain-containing mTORinteracting protein (DEPTOR), a natural mTOR inhibitor, remains unclear in this process. Here, it is reported that EGFR expression is significantly increased in tumors of lung adenocarcinoma patients and is negatively correlated with the expression of DEPTOR. Activation of EGFR signaling, by EGF, in A549 lung adenocarcinoma cells (overexpressing EGFR) significantly enhanced the function of the mTOR autoamplification loop, consisting of S6K, mTOR, CK1a, and bTrCP1, which resulted in downregulation of DEPTOR expression. Gefitinib, a specific EGFR inhibitor, stimulated DEPTOR accumulation by downregulating the function of the mTOR autoamplification loop. Furthermore, a series of assays conducted in DEPTOR knockout or ectopic expression in A549 cells confirmed that DEPTOR inhibited proliferation, migration, and invasion as well as the in vivo tumor growth of lung adenocarcinoma. Importantly, tumor progression mediated by EGFR ectopic expression was diminished by transfection with DEPTOR. This study uncovers the important inhibitory role of DEPTOR in lung adenocarcinoma progression and reveals a novel mechanism that EGFR downregulates DEPTOR expression to facilitate tumor growth.Implications: DEPTOR acts as a tumor suppressor by limiting EGFR-driven lung adenocarcinoma progression.