SETD1A-mediated H3K4me3 methylation upregulates lncRNA HOXC-AS3 and the binding of HOXC-AS3 to EP300 and increases EP300 stability to suppress the ferroptosis of NSCLC cells.

BACKGROUND: Histone methyltransferases are crucial regulators in non-small cell lung cancer (NSCLC) development. This study explored the mechanism of histone methyltransferase SET domain containing 1A (SETD1A)-mediated H3K4me2 methylation in NSCLC cell ferroptosis and provides novel targets for NSCLC treatment. METHODS: Upon downregulation of SETD1A in NSCLC cell lines, cell proliferation potential, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities, iron content, and SETD1A, long noncoding RNA HOXC cluster antisense RNA 3 (lncRNA HOXC-AS3), E1A binding protein p300 (EP300), glutathione peroxidase 4 (GPX4) expressions were determined via cell counting kit-8, ELISA, iron assay kits, RT-qPCR, and western blot. Enrichment levels of SETD1A and H3K4me3 in the HOXC-AS3 promotor were measured via chromatin immunoprecipitation, and the binding of HOXC-AS3 and EP300 was analyzed via RNA immunoprecipitation. Rescue experiments were performed to confirm their roles in NSCLC cell ferroptosis. Xenograft tumor models were established to validate the role of SETD1A in vivo. RESULTS: SETD1A, H3K4me3, HOXC-AS3, and EP300 were highly-expressed in NSCLC cells. Silencing SETD1A inhibited NSCLC cell proliferation, increased MDA and iron levels, and decreased SOD, GSH, and GPX4 levels. SETD1A downregulation reduced H3K4me3 level, HOXC-AS3 expression, the binding of HOXC-AS3 to EP300, and EP300 stability. Overexpression of HOXC-AS3 or EP300 reversed the promotion of silencing SETD1A on NSCLC cell ferroptosis. Silencing SETD1A reduced tumor volume and weight and positive rate of ki67 and increased ferroptosis through the HOXC-AS3/EP300 axis. CONCLUSION: SETD1A-mediated H3K4me2 methylation promoted HOXC-AS3 expression, binding of HOXC-AS3 to EP300, and EP300 stability, thereby suppressing NSCLC cell ferroptosis.

Let-7a targets Rsf-1 to modulate radiotherapy response of non-small cell lung cancer cells through Ras-MAPK pathway.

PURPOSE: Radiotherapy is the most commonly selective medical treatment for non-small cell lung cancer (NSCLC) and the multiple underlying mechanisms are considered as the effectively theoretical foundation. Herein, we investigated the effects of let-7a targets Rsf-1 on modulating the radiotherapy response in NSCLC cells by Ras-MAPK pathway. METHODS: A549 cells were divided into different groups to investigate the role of let-7a and Rsf-1 on the radiotherapy response. The expression of let-7a and Rsf-1 were detected by RT-PCR. Bioinformatic analysis indicated that Rsf-1 is the target of let-7a. The binding site of let-7a in the Rsf-1 3'UTR was detected based on double luciferase reporter assay and Western blot. The cell variability and proliferation were assessed by MTT and colony formation assay. The expression levels of Ras-MARK signaling pathway related proteins were assessed by RT-PCR. RESULTS: RT-PCR results showed that radiotherapy could up-regulate the expression of let-7a, thereby reducing the expression of Rsf-1, and the correlation between the two factors was negatively correlated. At the same time, let-7a overexpression and Rsf-1 silencing could further reduce the activity of A549 cells after radiotherapy, have an inhibitory effect on cell proliferation and inhibit the expression of related proteins in the Ras-MAPK pathway. CONCLUSIONS: Rsf-1 is the target of Let-7a. The present study provides evidence that let-7a targeting Rsf-1 can modulate radiotherapy response in NSCLC cells through Ras-MAPK pathway.

One successful primary closure case of bronchopleural fistula after pneumonectomy by a new method.

One case of successful primary closure of a bronchopleural fistula (BPF) after right pneumonectomy by sealing from both inside the chest cavity and bronchus is reported. The patient was a 47-year-old man who underwent right pneumonectomy due to right lung total collapse and atelectasis which was long-term compressed by a huge cyst inside the right chest cavity. A BPF was found on day 20 after surgery. A thoracotomy approach was performed because it was difficult to find an appropriate location for close drainage. Once the effusion and bloody coagulum was cleaned up from the right chest cavity, it was still difficult to find the bronchial stump because of the thick pleural fibrous membranes, and no visible fistula was found. Inside the chest cavity, a bright spot could be seen when the bronchoscope was inserted to the right bronchial stump. Anastomotic glue (OB Glue) was smeared on the bright spot and NEOVEIL (Gunze Co., Tokyo, Japan) was used to cover and reinforce the area. Meanwhile OB Glue (Gzbme Co., Guangzhou, China) was placed on the bronchial stump by bronchoscope. Closed drainage was performed after the operation. The patient recovered well having an uncomplicated postoperative course and was discharged 7 days after the treatment.

Overexpression of micro ribonucleic acid-591 inhibits cell proliferation and invasion of malignant pleural mesothelioma cells.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive cancer refractory to current therapies. Reduced expression of micro ribonucleic acid (miR)-591 in a range of cancer types has suggested it is a potent tumor suppressor, and overexpression has been shown to inhibit tumor cell growth. The role of miR-591 in MPM is largely unknown. METHODS: miR-591 was over-expressed in vitro using micro RNA mimics in three MPM cell lines (H513, H2052, H2373), and effects on tumor cell growth, proliferation, invasion, and target gene expression were assessed. RESULTS: miR-591 mimic was introduced into MPM cell lines to overexpress this microRNA. The cellular growth, proliferation, and invasive capability was significantly inhibited after overexpression of miR-591. Growth inhibition caused by miR-591 correlated with upregulation of p21 and Bax. Reduced invasive capability correlated with downregulation of matrix metalloproteinase-2 and transforming growth factor-ß1. CONCLUSION: miR-591 is a potent tumor suppressor in MPM. Overexpression of miR-591 may represent a novel therapeutic approach for MPM.

Corrosive induced carcinoma of esophagus after 58 years.

Patients with corrosive induced esophageal strictures have an increased risk of esophageal carcinoma. We present a case of a 61-year-old man who ingested sulfuric acid at the age of 3 years and then developed dysphagia at late follow-up. In 2010, he presented to the outpatient clinic with weight loss and worsening dysphagia to both solids and liquids. A barium swallow radiograph and endoscopy demonstrated a long stricture in the middle third of the esophagus. Ivor-Lewis esophagectomy was undertaken via an upper midline abdominal incision and a right thoracotomy, and pathologic examination of the resection specimen confirmed a well-differentiated esophageal squamous cell carcinoma. Twenty-two months postoperatively, he reports no dysphagia, and no tumor recurrence was evident during follow-up.

Neoadjuvant chemoradiotherapy could improve survival outcomes for esophageal carcinoma: a meta-analysis.

BACKGROUND: The effectiveness of neoadjuvant chemoradiotherapy in patients with resectable esophageal carcinoma remains controversial. AIMS: The purpose of this study was to assess the effect of neoadjuvant chemoradiotherapy on operable esophageal carcinoma. METHODS: We searched PubMed, EMBASE and Web of Science and identified all randomized controlled trials published up until July 2011 that directly compared chemoradiotherapy followed by surgery with surgery alone. The risk ratio (RR) with its corresponding 95 % confidence interval (CI) was the principal measure of effects. RESULTS: Twelve randomized controlled trials that met our inclusion criteria were identified. Chemoradiotherapy followed by surgery was associated with significantly improved 1-year (RR = 0.86, 95 % CI = 0.74-0.98, P = 0.03), 3-year (RR = 0.82, 95 % CI = 0.73-0.92, P = 0.0007) and 5-year (RR = 0.83, 95 % CI = 0.72-0.96, P = 0.01) survival times compared with surgery alone. Subgroup analysis suggested that this benefit was associated with concurrent chemoradiotherapy but not sequential chemoradiotherapy. Neoadjuvant chemoradiotherapy could improve 3- and 5-year survival outcomes for squamous cell carcinoma but not those for adenocarcinoma. Postoperative morbidity (RR = 0.97, 95 % CI = 0.86-1.09, P = 0.56) and mortality (RR = 1.56, 95 % CI = 0.97-2.50, P = 0.07) did not increase in patients treated by chemoradiotherapy. CONCLUSIONS: Our findings revealed that compared with surgery alone, neoadjuvant chemoradiotherapy was associated with improved 1-, 3- and 5-year survival times, but not associated with increased postoperative morbidity and mortality in patients with esophageal carcinoma.

Effects of RNAi-mediated matrix metalloproteinase-2 gene silencing on the invasiveness and adhesion of esophageal carcinoma cells, KYSE150.

BACKGROUND: Esophageal carcinoma is one of the main malignancies in China. Previous studies indicated that matrix metalloproteinases (MMPs) play important roles in the process of tumor invasion and metastasis in several types of solid tumors. Among all of the MMPs, MMP-2 is one of the MMPs closely associated with tumor invasion. In this study, we suppressed MMP-2 expression with RNA interference and then observed inhibitory effects on the invasion and migration of the esophageal carcinoma cell line KYSE150. METHODS: Three target sequences were selected and siRNA against MMP-2 mRNA were synthesized. After being transfected by the transfection complexes, the MMP-2 expression of KYSE150 cells, which overexpresses MMP-2, were examined by Western blot analysis and real-time polymerase chain reaction (PCR). Cell migration and invasion were measured with migration assay and Boyden chamber assays, respectively. RESULTS: RNAi against MMP-2 successfully inhibited the mRNA and protein expression of MMP-2 in the esophageal carcinoma cell line KYSE150. MMP-2 knockdown inhibited the invasion and migration of esophageal carcinoma cell line KYSE150. CONCLUSIONS: These findings suggested that the RNAi approach towards MMP-2 may be a potentially effective therapeutic method for the treatment of esophageal carcinoma.