Increasing evidence have proved that long noncoding RNAs (lncRNAs) play significant roles in tumorigenesis and development of various cancers. However, the effect of small nucleolar RNA host gene 20 (SNHG20) on the progression of esophageal squamous cell carcinoma (ESCC) remains to be discovered. Herein, we aim to find out the function and the possible mechanism of SNHG20 in ESCC progression. In our study, we demonstrate that SNHG20 is markedly upregulated in ESCC tissues and cell lines. Besides, the level of SNHG20 is closely associated with tumor size, lymph node metastasis, TNM stage, and tumor grade. In addition, SNHG20 level is an independent predictor for clinical outcomes of ESCC patients. Then the gain-and loss-of-function assays reveal that SNHG20 overexpression promotes cell proliferation, migration, invasion, and epithelialmesenchymal transition as well as represses apoptosis, whereas depletion of SNHG20 exhibits opposite effects. Moreover, we uncover that SNHG20 modulates the expression of ataxia telangiectasia-mutated kinase (p-ATM), p-JAK1/2, and programmed cell death 1 ligand 1 (PD-L1) in ESCC cells and ATM upregulation restores the suppressive effect of SNHG20 inhibition on ESCC progression. Therefore, we conclude that SNHG20 serves as a carcinogen in ESCC by promoting growth and metastasis via ATM-JAK-PD-L1 pathway, supplying a possibly effective therapeutic target for ESCC.
K E Y W O R D SATM-JAK-PD-L1 pathway, epithelial-mesenchymal transition, esophageal squamous cell carcinoma, metastasis, proliferation, small nucleolar RNA host gene 20
BackgroundEndoplasmic reticulum lipid raft-associated protein 2 (ERLIN2) is protein contained in the membrane of the endoplasmic reticulum. In lung adenocarcinoma (LUAD), the molecular function of ERLIN2 and the correlation between ERLIN2 and tumor-infiltrating immune cells have been unclear. The aim of our study was to determine the role of ERLIN2 in LUAD development to provide a better understanding of the molecular pathogenesis of this disease and identify new therapeutic targets for its treatment.MethodsImmunohistochemistry, Western blotting, and real-time quantitative polymerase chain reaction were used to detect protein and mRNA levels of ERLIN2 in LUAD and adjacent normal tissues. Using the A549, H1299 cell line, ERLIN2-short hairpin RNA was applied to silence ERLIN2 to determine its role in LUAD cell proliferation and invasion. Based on mRNA expression of ERLIN2 from the Cancer Genome Atlas (TCGA) database, we identified ERLIN2-related protein-coding genes and analyzed the Kyoto Encyclopedia of Genes and Genomes pathway to explore its potential biological functions and determined the correlation between ERLIN2 and tumor-infiltrating immune cells.ResultsERLIN2 was abnormally expressed in a variety of tumor tissues and is highly expressed in LUAD. This overexpression was associated with histological grade (P = 0.044), TNM stage (P = 0.01), and lymph node metastasis (P = 0.038). Patient overall survival was poorer with ERLIN2 overexpression. Downregulation of ERLIN2 inhibited LUAD cell proliferation and invasion in vitro. Based on mRNA expression of ERLIN2 from the TCGA database, 13 ERLIN2-related genes and 10 pathways were identified and showed a correlation between ERLIN2 and naive B cells and neutrophils.ConclusionERLIN2 could serve as a potential diagnostic and prognostic biomarker for LUAD and has demonstrated to be correlated with immune infiltrates, which suggests that it may represent a new therapeutic target for LUAD.
The maximum diameter of the balloon used for balloon dilatation(BD) of esophagogastric anastomotic stricture (EAS) is generally 20 millimeters. This study aimed to evaluate the safety and efficacy of BD under fluoroscopy, using balloons with a diameter of 25-30 millimeters. We retrospectively analyzed the data of patients with benign EAS treated by large BD (balloon diameter, 25-30 mm) under fluoroscopy. The Cox proportional hazards model (PHM) was used to identify the factors associated with stricture-free survival. The results show that a total of 127 patients were included in this study, and 204 BDs were performed. The technical success rate was 96.6%, and the clinical success rate was 99.2%. The incidence of serious adverse events was 3.4% (7/204). One patient died of massive hemorrhage during BD, and nine patients were lost to follow-up. For the remaining 117 patients, the median stricture-free survival period was 14.9 months. In multivariable analysis using the Cox PHM, only balloon diameter was significantly associated with stricture-free survival. The stricture-free survival period tended to increase as balloon diameter increased. Large BD under fluoroscopy appears to be safe and effective for the treatment of benign EAS after esophagectomy.
BackgroundNeoplastic esophagogastric anastomotic strictures after resection of esophageal cancer is a very difficult problem in clinical practice. We aim at to investigate the safety and feasibility of arterial infusion chemotherapy in treatment of neoplastic esophagogastric anastomotic strictures after esophagectomy.MethodsFrom October 2014 to December 2019, 50 patients with Neoplastic esophagogastric anastomotic strictures after resection of esophageal cancer were assessed retrospectively. Preoperative dysphagia was grade III in 34 cases and grade IV in 16 cases. Thirty-eight patients had different degrees of dyspnea before surgery Twenty-five patients had intolerable (grade IV) dyspnea and airway stenting was undertaken before surgery. Thirteen patients had tolerable dyspnea that did not require airway stenting, and preoperative dyspnea was grade III.ResultsAll patients were successfully treated with arterial infusion chemotherapy, no paraplegia or death occurred. The dysphagia grade of 50 patients after AIC was compared: one case had grade I, 40 cases had grade II, and nine cases had grade III. Thirteen patients had tolerable dyspnea that did not necessitate airway stenting. Dyspnea was classified as grade I in five cases and grade II in eight cases. After 1–3 courses of AIC, 50 patients were followed up for a complete response (eight cases), partial response (28) and stable disease (14 cases). Total objective effective rate (complete response+ partial response) and disease control rate(complete response + partial response + stable disease)were 72.0% and 100.0%, respectively. The median duration of follow-up was 8.5 months. One-year survival was 46.0%.ConclusionArterial infusion chemotherapy is safe and efficacious treatment for Neoplastic esophagogastric anastomotic strictures after esophagectomy.
The present study aimed to define the tumor-suppressive role of microRNA-499 (miR-499) in lung cancer cells and its underlying mechanism. First, qRT-PCR analysis revealed poor expression of miR-499 in clinical samples and cell lines of lung cancer. Next, we performed loss-and gain-of-function experiments for the expression of miR-499 in lung cancer cells exposed to irradiation (IR) to determine the effect of miR-499 expression on cell viability and apoptosis as well as tumor growth. Results showed that overexpression of miR-499 inhibited cell viability, enhanced the radiosensitivity of lung cancer cells, and promoted cell apoptosis under IR. Furthermore, CK2a was verified to be a target of miR-499, and miR-499 was identified to repress p65 phosphorylation by downregulating CK2a expression, which ultimately diminished the survival rate of lung cancer cells under IR. Collectively, the key findings of the study illustrate the tumor-inhibiting function of miR-499 and confirmed that miR-499-mediated CK2a inhibition and altered p65 phosphorylation enhances the sensitivity of lung cancer cells to IR.
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