RESUMEN
Gastric cancer stem cells (GCSCs) play critical roles in gastric cancer (GC) initiation and development. Circular RNAs (circRNAs) participate in diverse cancer biological processes and function as tumor suppressors or oncogenes. This study aims to discover the expression profile and functional roles of circRNAs in GCSCs. A spheroid formation assay was conducted to enrich GCSCs. Genome-wide sequencing of circRNAs showed that a novel circRNA, circSLC4A7, was one of the most upregulated circRNAs in GCSCs. CircSLC4A7 was localized to the nucleus, and its level was elevated in GC cells and tissues. Furthermore, circSLC4A7 increased CSC-like properties and drove cell proliferation, migration, and invasion, which were determined by gain- and loss-of-function experiments. Specific circRNA pull-down assays followed by mass spectrometry analysis, RNA immunoprecipitation, and dual RNA-fluorescence in situ hybridization and immunofluorescence assay were conducted and HSP90 was detected to interact with circSLC4A7 and mediate the oncogenic function of circSLC4A7 by activating the Notch1 signaling pathway in GC. This study highlights a novel oncogenic function of circSLC4A7 mediated by its binding with HSP90 and thus activating the Notch1 signaling pathway.
Asunto(s)
MicroARNs , Neoplasias Gástricas , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Neoplasias Gástricas/patología , Hibridación Fluorescente in Situ , Línea Celular Tumoral , ARN/genética , Transducción de Señal , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Receptor Notch1/genética , Receptor Notch1/metabolismoRESUMEN
AIM: Rectal stenosis is a relatively rare complication after transanal endoscopic microsurgery (TEM). This study aims to identify the predictive parameters for stenosis and the application of TEM in the treatment. METHOD: The clinical data of patients who underwent TEM for rectal adenoma and early cancer from 2008 to 2019 were retrospectively reviewed. We compared the clinicopathological characteristics of patients with stenosis and those without stenosis and analysed the risk factors for stenosis. Treatment outcomes of stenosis with TEM were evaluated. RESULTS: A total of 230 patients were enrolled in this study. Overall, the postoperative complication rate was 11.7% (27/230), including eight (3.5%) patients with stenosis. Patients with stenosis exhibited a higher rate of tumour showing a laterally spreading morphology (P = 0.048), a wider circumferential extent of mucosal defect (P < 0.001), a shorter distance of the tumour from the anal verge (P = 0.001) and a wider longitudinal extent of mucosal defect (P = 0.027). A circumferential extent of mucosal defect >3/4 (OR 94.945, 95% CI 3.611-2496.41, P = 0.006) was identified as the only independent risk factor for stenosis. The four patients with both stenosis and clinical symptoms were treated by incising the stenosis ring using the TEM platform; the stenosis was cured, and symptoms disappeared after one to four courses of treatment. CONCLUSIONS: Circumferential extent of mucosal defect ≥3/4 was an independent risk factor for stenosis in treating rectal adenoma and early cancer with TEM. Incision of the stenosis ring using the TEM platform is an effective strategy for treating stenosis.