Background: Circular RNAs (circ-RNAs) have been demonstrated to influence initiation, drug resistance, and metastasis of tumors. However, the effects of circular-phosphoglycerate mutase 1 (circ-PGAM1) on matrine resistance in nonsmall cell lung cancer (NSCLC) remain unknown. Materials and Methods: The reverse transcription–quantitative polymerase chain reaction (RT-qPCR) was used to determine gene expression. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and cell colony formation assays were used to evaluate NSCLC apoptosis and cell proliferation after indicated treatments, respectively. Results: circ-PGAM1 was upregulated in human NSCLC cell lines (H1299 and A549) compared with the human normal lung epithelial (BEAS-2B) cells. circ-PGAM1 overexpression reversed the matrine treatment-induced inhibition on proliferation of NSCLC cells (A549 and H1299) and rescued the matrine treatment-stimulated apoptosis of these cells. miR-326 was demonstrated to interact with circ-PGAM1. circ-PGAM1 knockdown enhanced the antitumor effect of matrine on NSCLC cell proliferation and apoptosis, which was reversed by miR-326 inhibition. The authors also identified CXCR5 as a key downstream target of miR-326 in A549 cells. Conclusions: circ-PGAM1 enhances matrine resistance of NSCLC cells through the miR-326/CXCR5 axis. The authors' findings provide new insights into NSCLC-targeted therapy.
Background: Lung cancer (LC) represents a leading cause of cancer-related deaths. The aim of this study was to analyze the application value of ZIC5 in the prognosis evaluation of LC. Materials and Methods: The mRNA and protein levels of ZIC5 in LC tissues and adjacent normal controls were detected by quantitative real-time polymerase chain reaction and Western blot analysis, respectively. Chi-square test was performed to estimate the association between ZIC5 expression and clinical features. Furthermore, overall survival (OS) curves were plotted using Kaplan–Meier method with log rank test. The prognosis analysis was analyzed using Cox proportional hazards model. Results: Compared with that of noncancerous tissues, the expression of ZIC5 in LC tissues was significantly increased at both protein and mRNA levels (p < 0.001). Moreover, ZIC5 expression showed a positive correlation with differentiation (p = 0.001) and tumor size (p = 0.016). Survival analysis suggested that high expression of ZIC5 predicted shorter OS (log rank test, p = 0.007). ZIC5 might be an independent prognostic biomarker for LC (hazard ratio = 2.892; 95% confidence interval, 1.297–6.449; p = 0.009). Conclusions:ZIC5 expression is upregulated in LC, and it may be employed as a prognostic biomarker for patients with LC.
Purpose: To explore the effects of hypoxic non-small-cell lung cancer (NSCLC)-derived exosomes on NSCLC resistance to cisplatin. Materials and methods: Exosomes were isolated by differential centrifugation and characterized by transmission electron microscope and Western blotting. Quantitative real-time PCR was used to measure miR-21 levels. MTT assays and colony formation assays were performed to investigate the effects of hypoxia-induced exosomes on cisplatin resistance. Results: Hypoxic NSCLC cell-derived exosomes facilitate normoxic cell resistance to cisplatin. In addition, hypoxia enhanced the miR-21 expression in NSCLC cells and cell-derived exosomes. Interestingly, changes in miR-21 levels in the hypoxia-induced exosomes affected the sensitivity of recipient cells to cisplatin. Mechanically, exosomal miR-21 promoted cisplatin resistance by downregulating phosphatase and tensin homolog (PTEN). The expression of miR-21 in tumor cell lines and clinical NSCLC tumor samples was positively correlated with hypoxia-inducible factor-1α and negatively correlated with PTEN. Moreover, high miR-21 expression was associated with shorter median survival period in patients undergoing pharmacotherapy, but no association was observed in patients who were not under pharmacotherapy. Conclusion: Exosomal miR-21 derived from hypoxic NSCLC cells may promote cisplatin resistance, which indicates that exosomal miR-21 might be a potential biomarker and therapeutic target to address NSCLC chemoresistance. Keywords: non-small-cell lung cancer, exosomes, miR-21, cisplatin resistance, PTEN
Cisplatin (DDP) resistance is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). MicroRNA-219a-5p (miR-219a-5p) has been reported to be a tumor suppressor in several cancers, but whether it regulates chemosensitivity in NSCLC remains unclear. Here, using quantitative real time PCR analysis, we observed that miR-219a-5p was down-regulated in responding tumor tissues compared with that in non-responding tumor tissues from NSCLC patients received DDP-based chemotherapy. Consistently, miR-219a-5p expression was lower in cisplatin (DDP)-resistant NSCLC cell lines (A549-R and SPC-A1-R) than that in corresponding parental cells (A549 and SPC-A1). Gain of-function assay showed ectopic expression of miR-219a-5p reversed DDP chemoresistance of NSCLC cells in vitro and in vivo. Using bioinformatics prediction and dual-luciferase reporter assays, we identified the FGF9 gene as a novel direct target of miR-219a-5p. Moreover, restoration of FGF9 expression reversed the miR-219a-5p-mediated chemosensitivity. In conclusion, this study demonstrated miR-219a-5p plays a crucial role in the development of acquired drug resistance to DDP in NSCLC cells by targeting FGF9 and might be a therapeutic target for DDP resistance in clinical practice.
Objective
To describe the technique and outcomes for an initial series of 200 cases of lobectomy and segmentectomy using single-intercostal two-port video-assisted thoracoscopic surgery(VATS), and investigate the effect of this technique on postoperative chronic pain.
Methods
Between June 2014 and August 2015, 217 consecutive patients attempted lobectomy and segmentectomy using single-intercostal two-port VATS. Between January 2014 and June 2014, the same surgeon continuously completed 80 cases of lobectomy and segmentectomy using three-port approach. The clinical data of all these patients were retrospectively analyzed, including the data on chronic pain at the follow-up 6 months after operation.
Results
Among the 217 patients attempting lobectomy and segmentectomy using single-intercostal two-port VATS, 200 patients(173 cases of primary lung cancer and 27 cases of benign diseases) successfully completed the operation(141 cases of lobectomy and 59 cases of segmentectomy), and the other 17 patients transferred to three-port approach or open surgery due to various reasons. Of these 200 patients, the mean duration of surgery was (160.1 ± 56.1) min, the mean number of lymph node dissection was 10.5 ± 5.3, the mean duration of hospitalization after operation was (6.4 ± 2.9)d, complications occurred in 46 patients, and 1 patient died within 30 d after surgery. A total of 92 patients undergoing single-intercostal two-port VATS and 71 patients with three-port approach were successfully followed up 6 months after surgery, the prevalence of chronic pain and the mean chronic pain score of the former were significantly lower than that of the latter[25.0% vs 43.7%, χ2=6.300, P=0.012; (2.3±0.8) vs (3.6±1.6), t=3.912, P<0.001].
Conclusions
Lobectomy and segmentectomy using single-intercostal two-port VATS is safe and feasible for most patients. Compared with three-port approach, this technique significantly reduces the prevalence and score of chronic pain.
Key words:
Video-assisted thoracoscopic surgery; Lobectomy; Lung segmentectomy; Chronic pain
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