LKB1 prevents ILC2 exhaustion to enhance antitumor immunity.

Group 2 innate lymphoid cells (ILC2s) play crucial roles in mediating allergic inflammation. Recent studies also indicate their involvement in regulating tumor immunity. The tumor suppressor liver kinase B1 (LKB1) inactivating mutations are associated with a variety of human cancers; however, the role of LKB1 in ILC2 function and ILC2-mediated tumor immunity remains unknown. Here, we show that ablation of LKB1 in ILC2s results in an exhausted-like phenotype, which promotes the development of lung melanoma metastasis. Mechanistically, LKB1 deficiency leads to a marked increase in the expression of programmed cell death protein-1 (PD-1) in ILC2s through the activation of the nuclear factor of activated T cell pathway. Blockade of PD-1 can restore the effector functions of LKB1-deficient ILC2s, leading to enhanced antitumor immune responses in vivo. Together, our results reveal that LKB1 acts to restrain the exhausted state of ILC2 to maintain immune homeostasis and antitumor immunity.

Real-time, random-access organ screening for carbapenem-resistant organisms (CRO) reduces CRO-associated, donor-derived infection mortality in lung transplant recipients.

PURPOSE: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality. METHODS: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups. RESULTS: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03). CONCLUSION: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation.

Case report: Complete resection of invasive thymoma invading the superior vena cava and right atrium under cardiopulmonary bypass support.

Here we describe an uncommon case of a 48-year-old male patient with an invasive thymoma invading the superior vena cava, bilateral innominate veins, right internal jugular vein, right subclavian vein, right atrium, azygos vein, and part of the lung tissues. The tumor was resected entirely under cardiopulmonary bypass support, and the venous bypass using a vascular graft was successfully established between the left innominate vein and the right atrium. The postoperative course was uneventful, and the patient was discharged 15 days after surgery without complications.

Identification of Sports Athletes' High-Strength Sports Injuries Based on NMR.

In order to study the high-strength sports injury in sports, this paper proposes a method based on NMR to identify the high-strength sports injury of sports athletes. This method carries out a questionnaire survey and research on the athletes who are excellent in sports dance major from 2019 to 2021 in the Institute of Physical Education. The athletes' age range is 18-25 years, and the training period of sports dance is 3-5 years. The results show that compared with other recognition methods, the recognition method based on NMR has higher accuracy and efficiency. The method of this study is helpful to improve the recognition efficiency and accuracy. Athletes are very easy to get injured during sports. In order to reduce the degree of injury of athletes, we should strictly follow the action standards in the training process to avoid serious injury.

Sparse group selection and analysis of function-related residue for protein-state recognition.

Machine learning methods have helped to advance wide range of scientific and technological field in recent years, including computational chemistry. As the chemical systems could become complex with high dimension, feature selection could be critical but challenging to develop reliable machine learning based prediction models, especially for proteins as bio-macromolecules. In this study, we applied sparse group lasso (SGL) method as a general feature selection method to develop classification model for an allosteric protein in different functional states. This results into a much improved model with comparable accuracy (Acc) and only 28 selected features comparing to 289 selected features from a previous study. The Acc achieves 91.50% with 1936 selected feature, which is far higher than that of baseline methods. In addition, grouping protein amino acids into secondary structures provides additional interpretability of the selected features. The selected features are verified as associated with key allosteric residues through comparison with both experimental and computational works about the model protein, and demonstrate the effectiveness and necessity of applying rigorous feature selection and evaluation methods on complex chemical systems.

Circular RNA circRNA-0039459 promotes the migration, invasion, and proliferation of liver cancer cells through the adsorption of miR-432.

This study aimed to investigate the molecular mechanism of circular RNA circ-0039459 and its effects on the apoptosis, proliferation, invasion, and migration of hepatocellular carcinoma cells. The expression of circ-0039459, miR-432, and synoviolin 1 (SYVN1) mRNA was determined using real-time quantitative reverse transcription PCR. Cell proliferation was detected by cell counting kit-8 assay, and the apoptosis rate was detected using flow cytometry. Cell migration and invasion were detected using Transwell assay. The expression of E-cadherin, N-cadherin, and vimentin was detected using western blot. The targeting relationship between circ-0039459 and miR-432 as well as that between miR-432 and SYVN1 were detected using the dual-luciferase reporter and RNA pull-down assays. We found that circ-0039459 and SYVN1 mRNA were highly expressed, whereas miR-432 was lowly expressed in hepatocellular carcinoma cells and tissues. After treatment with ribonuclease R or actinomycin D, the expression of linear RNA was reduced, whereas that of circular RNA was not significantly changed. circ-0039459 knockdown or miR-432 overexpression can inhibit cell proliferation, invasion, and migration and the expression of N-cadherin and vimentin proteins in carcinoma cells as well as promote apoptosis and increase the E-cadherin level. circ-0039459 targeted and regulated miR-432, which targeted and regulated SYVN1. The decreased miR-432 expression reversed the effects of circ-0039459 knockout in cancer cells. Furthermore, SYVN1 overexpression reversed the effect of miR-432 overexpression in hepatoma cells. Hence, circ-0039459 can affect the proliferation, apoptosis, migration, and invasion of hepatocellular carcinoma cells through the adsorption of miR-432, thereby regulating the expression of SYVN1.

The correlation between lncRNA NEAT1 and serum hepcidin in the peripheral blood of non-alcoholic fatty liver disease patients.

OBJECTIVES: To explore and analyze the correlation between lncRNA NEAT1 and serum hepcidin (HEPC) in the peripheral blood of non-alcoholic fatty liver disease patients. METHODS: 119 patients, confirmed to have non-alcoholic fatty liver disease (NAFLD) and admitted to our hospital from January 2017 to June 2019, were enrolled in the NAFLD group, and 100 healthy subjects during the same period were enrolled in the control group. We recorded the two groups' general information and routine laboratory examination results and performed correlation analyses on the lncRNA NEAT1 expressions in their peripheral blood mononuclear cells (PBMCs) and HEPC. RESULTS: The BMI, the waist circumferences, and the ALT, GGT, TC, and TG levels in the NAFLD group were critically higher than they were in the control group (P<0.05). The relative expressions of lncRNA NEAT1 in the PBMCs of the NAFLD group were remarkably higher than they were in the control group (P<0.05). The HEPC levels in the NAFLD group were significantly higher than they were in the control group (P<0.05). The lncRNA NEAT1 expressions in the NAFLD patients presented a remarkable positive correlation with the ALT, GGT, TC, and TG levels (P<0.05). The HEPC levels were positively correlated with the ALT, GGT, TC, and TG levels in the NAFLD patients (P<0.05), and the lncRNA NEAT1 expressions in the peripheral blood had a positive correlation with HEPC (P<0.05). We used ROC curves to analyze the diagnostic value of lncRNA NEAT1 in the peripheral blood to NAFLD, and the area under the curve was 0.822 (95% confidence interval of overall probability: 0.612~0.921). The sensitivity was 86.47%, and the specificity was 82.03%. CONCLUSION: lncRNA NEAT1 is abnormally overexpressed in the PBMCs of patients with NAFLD. The regulatory effect of lncRNA NEAT1 on NAFLD may be related to the mechanism of HEPC, which is expected to be a potential biological indicator for the prevention and treatment of NAFLD.

Neuropilin-1 mediates lung tissue-specific control of ILC2 function in type 2 immunity.

Group 2 innate lymphoid cells (ILC2s) are highly heterogeneous tissue-resident lymphocytes that regulate inflammation and tissue homeostasis in health and disease. However, how these cells integrate into the tissue microenvironment to perform tissue-specific functions is unclear. Here, we show neuropilin-1 (Nrp1), which is induced postnatally and sustained by lung-derived transforming growth factor beta-1 (TGFß1), is a tissue-specific marker of lung ILC2s. Genetic ablation or pharmacological inhibition of Nrp1 suppresses IL-5 and IL-13 production by ILC2s and protects mice from the development of pulmonary fibrosis. Mechanistically, TGFß1-Nrp1 signaling enhances ILC2 function and type 2 immunity by upregulating IL-33 receptor ST2 expression. These findings identify Nrp1 as a tissue-specific regulator of lung-resident ILC2s and highlight Nrp1 as a potential therapeutic target for pulmonary fibrosis.

Ischemia-Reperfusion Injury in a Simulated Lung Transplant Setting Differentially Regulates Transcriptomic Profiles between Human Lung Endothelial and Epithelial Cells.

Current understanding of mechanisms of ischemia-reperfusion-induced lung injury during lung preservation and transplantation is mainly based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic times (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with a serum containing culture medium to simulate lung transplantation. Cell morphology, viability, and transcriptomic profiles were studied. Ischemia-reperfusion injury induced a CIT time-dependent cell death, which was associated with dramatic changes in gene expression. Under normal control conditions, endothelial cells showed gene clusters enriched in the vascular process and inflammation, while epithelial cells showed gene clusters enriched in protein biosynthesis and metabolism. CIT 6 h alone or after reperfusion had little effect on these phenotypic characteristics. After CIT 18 h, protein-biosynthesis-related gene clusters disappeared in epithelial cells; after reperfusion, metabolism-related gene clusters in epithelial cells and multiple gene clusters in the endothelial cells also disappeared. Human pulmonary endothelial and epithelial cells have distinct phenotypic transcriptomic signatures. Severe cellular injury reduces these gene expression signatures in a cell-type-dependent manner. Therapeutics that preserve these transcriptomic signatures may represent new treatment to prevent acute lung injury during lung transplantation.

A Novel Circular RNA circCSPP1 Promotes Liver Cancer Progression by Sponging miR-1182.

INTRODUCTION: Aberrant circular RNA (circRNA) expression has been extensively discovered for its involvement in both the initiation and progression of various cancers. Through screening circRNA profile, we identified a novel circRNA has_circ_0001806, which is termed as circCSPP1 in liver cancer. In the present study, we aim to investigate the role of circCSPP1 in the progression of liver cancer. METHODS: Fluorescence in situ hybridization (FISH) was used to detect the location of circCSPP1. Function studies including MTT, colony formation assay, transwell assay and flow cytometry were carried out to detect the malignant behaviour of circCSPP1 on liver cancer cells. Luciferase assay and RNA pull down were used to detect the interaction between miR-1182 and circCSPP1 as well as RAB15. Quantitative realtime (qPCR) and Western blot were performed to evaluate the RNA and protein expression, respectively. RESULTS: CircCSPP1 knockdown inhibited the proliferation, migration and invasion while promoted apoptosis of liver cancer cells. Mechanically, we predicted and verified the target miR of circCSPP1 which is miR-1182. miR-1182 was capable of reversing the effect of circCSPP1 on liver cancer cells. Moreover, miR-1182 was found to also target RAB15 to participate in the regulation of cell phenotype. DISCUSSION: Taken together, circCSPP1 promoted progression of liver cancer cells via sponging miR-1182 which may serve as a novel prognostic and therapeutic target for liver cancer.

Glucagon-like peptide-1 receptor mediates the beneficial effect of liraglutide in an acute lung injury mouse model involving the thioredoxin-interacting protein.

Repurposing clinically used drugs is among the important strategies in drug discovery. Glucagon-like peptide-1 (GLP-1) and its diabetes-based drugs, such as liraglutide, possess a spectrum of extra-pancreatic functions, while GLP-1 receptor (GLP-1R) is most abundantly expressed in the lung. Recent studies have suggested that GLP-1-based drugs exert beneficial effects in chronic, as well as acute, lung injury rodent models. Here, we show that liraglutide pretreatment reduced LPS induced acute lung injury in mice. It significantly reduced lung injury score, wet/dry lung weight ratio, bronchoalveolar lavage fluid immune cell count and protein concentration, and cell apoptosis in the lung, and it was associated with reduced lung inflammatory cytokine and chemokine gene expression. Importantly, these effects were virtually absent in GLP-1R-/- mice. A well-known function of GLP-1 and GLP-based drugs in pancreatic ß-cells is the attenuation of high-glucose stimulated expression of thioredoxin-interacting protein (TxNIP), a key component of inflammasome. LPS-challenged lungs showed elevated TxNIP mRNA and protein expression, which was attenuated by liraglutide treatment in a GLP-1R-dependent manner. Hence, our observations suggest that GLP-1R is essential in mediating beneficial effects of liraglutide in acute lung injury, with the inflammasome component TxNIP as a potential target.

HDAC6-specific inhibitor suppresses Th17 cell function via the HIF-1α pathway in acute lung allograft rejection in mice.

Background: Previous animal experiments and clinical studies indicated the critical role of Th17 cells in lung transplant rejection. Therefore, the downregulation of Th17 cell function in lung transplant recipients is of great interest. Methods: We established an orthotopic mouse lung transplantation model to investigate the role of histone deacetylase 6-specific inhibitor (HDAC6i), Tubastatin A, in the suppression of Th17 cells and attenuation of pathologic lesions in lung allografts. Moreover, mechanism studies were conducted in vitro. Results: Tubastatin A downregulated Th17 cell function in acute lung allograft rejection, prolonged the survival of lung allografts, and attenuated acute rejection by suppressing Th17 cell accumulation. Consistently, exogenous IL-17A supplementation eliminated the protective effect of Tubastatin A. Also, hypoxia-inducible factor-1α (HIF-1α) was overexpressed in a lung transplantation mouse model. HIF-1α deficiency suppressed Th17 cell function and attenuated lung allograft rejection by downregulating retinoic acid-related orphan receptor γt (ROR γt) expression. We showed that HDAC6i downregulated HIF-1α transcriptional activity under Th17-skewing conditions in vitro and promoted HIF-1α protein degradation in lung allografts. HDAC6i did not affect the suppression of HIF-1α-/- naïve CD4+ T cell differentiation into Th17 cell and attenuation of acute lung allograft rejection in HIF-1α-deficient recipient mice. Conclusion: These findings suggest that Tubastatin A downregulates Th17 cell function and suppresses acute lung allograft rejection, at least partially, via the HIF-1α/ RORγt pathway.

Comprehensive analysis of differentially expressed long non-coding RNAs in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the primary subtype of lung cancer. Long non-coding RNAs (lncRNAs) have been reported to serve prominent roles in cancer progression. However, the expression patterns and potential roles of lncRNAs in NSCLC remain to be elucidated. In the present study, four public datasets were analyzed to identify differentially expressed lncRNAs (DElncs) in NSCLC. A further dataset, GSE19188, was analyzed to validate the findings. A total of 38 upregulated and 31 downregulated lncRNAs were identified in NSCLC, compared with samples from healthy controls. Among these, 12 lncRNAs were associated with the progression of NSCLC, and dysregulated between high grade (stage III and IV) and low grade (stage II) NSCLC samples. Moreover, dysregulation of lncRNA-SIGLEC17P, GGTA1P, A2M-AS1, LINC00938, GVINP1, LINC00667 and TMPO-AS1 was associated with overall survival time in patients with NSCLC. Co-expression analyses, combined with the construction of protein-protein interaction networks, were performed to reveal the potential roles of key lncRNAs in NSCLC. The present study revealed a series of lncRNAs involved in the progression of NSCLS, which may serve as novel biomarkers for the disease.

Treatment-related severe and fatal adverse events with molecular targeted agents in the treatment of advanced gastric cancer: a meta-analysis.

AIM: To perform a systematic review and meta-analysis of Phase III randomized controlled trials (RCTs) to determine the incidence and risk of severe adverse events (AEs) with molecular targeted agents (MTAs) in advanced/metastatic gastric cancer (GC) patients. METHODS: A comprehensive literature search for related trials published up to December 2015 was performed. Eligible studies were Phase III RCTs of advanced/metastatic GC patients assigned to MTAs or control group. Data were extracted by two authors for severe and fatal AEs (FAEs). RESULTS: A total of nine Phase III RCTs involved 4,934 GC patients were ultimately identified. The pooled results demonstrated that the addition of TAs to therapies in advanced GC significantly increased the risk of developing severe AEs (relative risk: 1.12, 95% confidence interval: 1.02-1.24, P=0.02), but not for FAEs (relative risk: 0.97, 95% confidence interval: 0.65-1.45, P=0.88). Additionally, the most common causes of FAEs with MTAs were infections (16.3%), gastrointestinal hemorrhage (8.2%), and arterial thromboembolic events (8.2%), respectively. CONCLUSION: With available evidence, the use of TAs in GC patients was associated with an increased risk of severe AEs, but not for FAE. Clinicians should be aware of the risk of severe AEs with the administration of these drugs in these patients.

The Critical Role of Induced CD4+ FoxP3+ Regulatory Cells in Suppression of Interleukin-17 Production and Attenuation of Mouse Orthotopic Lung Allograft Rejection.

BACKGROUND: Lung transplantation is the only definitive therapy for many forms of end-stage lung disease. Studies have demonstrated the critical role of interleukin (IL)-17 in the development of lung rejection. Regulatory T cells (Tregs) are essential for the establishment and maintenance of immune tolerance. METHODS: We established mouse orthotopic lung transplantation models to investigate the importance of IL-17 and IL-17-producing cell types in acute lung allograft rejection and the efficacy of the adoptive transfer of induced Tregs (iTregs) in attenuating pathologic lesions of lung allografts. RESULTS: We found that the IL-17 produced by Th17 cells and γδ T cells might make the primary contributions to the progression of acute lung allograft rejection. Interleukin-17 deficiency decreased lung allograft lesions. Exogenous iTregs maintained their FoxP3 expression levels in lung allograft recipients. Induced Tregs therapy downregulated the expressions of Th17 and IL-17 γδ T cells and increased IL-10 production in the mouse orthotopic lung transplantation models. Moreover, the adoptive transfer of iTregs prolonged the survivals of the lung allografts and attenuated the progression of acute rejection. CONCLUSION: These data suggested that the adoptive transfer of iTregs could suppress the Th17 cells and IL-17 γδ cells of the recipients, decrease the expression of IL-17, and attenuate the pathology of acute lung allograft rejection. Exogenous iTregs upregulated immunosuppressive factors, such as IL-10 and suppressed IL-17-producing cells, which was one of the pathways to play a role in protecting lung allografts.

Effect of Th17 and Treg axis disorder on outcomes of pulmonary arterial hypertension in connective tissue diseases.

This prospective cohort study is to verify the hypothesis that the balance of Th17 and Treg cells frequencies in the peripheral circulation is disturbed in patients with varying degrees of connective tissue diseases-associated pulmonary arterial hypertension (CTD-aPAH) and to prove the influence of Th17/Treg imbalance on prognosis. We detected the frequencies and absolute counts of Th17 and Treg cells and related serum cytokines secretion and expressions of key transcription factors in 117 patients with connective tissue diseases (CTD), 53 patients with CTD-aPAH, and 48 healthy volunteers. Moreover, the median value according to levels of Th17/Treg ratios in patients with CTD-aPAH was chosen as basis of group division for survival analysis. CTD-aPAH patients revealed significant increase in peripheral Th17 cells, Th17-related cytokines, and ROR γt mRNA levels. They also presented a significant decrease in Treg cells, Treg-related cytokines, and Foxp3 mRNA levels as compared with CTD patients and healthy controls. More importantly, the Th17/Treg ratio was significantly related to the severity and prognosis of CTD-aPAH. This study indicated that the Th17/Treg axis disorder plays a critical role in CTD-aPAH. Furthermore, the dynamic balance between Th17 and Treg cells was likely to influence prognosis of patients with CTD-aPAH.

Analysis of predictive factors for postoperative survival for non small cell lung carcinoma patients with unexpected mediastinal lymph nodes metastasis.

OBJECTIVES: To discuss the predictive factors of postoperative survival for non small cell lung carcinoma (NSCLC) patients with clinical N0 stage but postoperative pathological N2 stage (cN0-pN2). METHODS: From January 1, 2005, to December 31, 2009, the clinical data of NSCLC patients with cN0-pN2 after radical surgery were retrospectively collected, and their survival information was collected through follow-up. The expiration date for follow-up was December 31, 2011. The predictive factors of postoperative survival for NSCLC patients with unexpected mediastinal lymph node metastasis were analyzed using Cox proportional hazards regression. RESULTS: A total of 263 patients were enrolled. The follow-up rate was 91.63%. The overall 1-, 3-, and 5-year survival rates were 94.6, 55.2, and 26.3%, respectively. Video-assisted thoracotomy surgery (VATS; odds ratio [OR] 0.659; 95% confidence interval [CI] 0.469 to 0.927; p = 0.017), multiple stations of metastatic mediastinal lymph nodes (OR 1.605; 95% CI 1.180 to 2.183; p = 0.003), and no adjuvant chemotherapy (OR 1.576; 95% CI 1.105 to 2.246; p = 0.012) were independent predictive factors for unexpected N2 patients. The median survival after VATS was superior to that after thoracotomy for patients with a single station of metastatic mediastinal lymph node (48.45 m vs 37.34 m, p = 0.018). The median survival without any adjuvant chemotherapy was inferior to that after adjuvant chemotherapy for patients with multiple stations of metastatic mediastinal lymph nodes (20.32 m vs 31.55 m, p = 0.001). CONCLUSION: The postoperative survival for NSCLC patients with cN0-pN2 was related to operational method, adjuvant chemotherapy, and the number of metastatic mediastinal lymph node stations. Patients with a single station of metastatic mediastinal lymph node are likely to benefit from VATS, whereas patients with multiple stations of metastatic mediastinal lymph nodes are likely to benefit from adjuvant chemotherapy.

Feasibility and long-term efficacy of video-assisted thoracic surgery for unexpected pathologic N2 disease in non-small cell lung cancer.

OBJECTIVES: This study compares early and late outcomes for treatment by video-assisted thoracic surgery (VATS) versus treatment by thoracotomy for clinical N0, but post-operatively unexpected, pathologic N2 disease (cN0-pN2). METHODS: Clinical records of patients with unexpected N2 non-small cell lung cancer (NSCLC) who underwent VATS were retrospectively reviewed, and their early and late outcomes were compared to those of patients undergoing conventional thoracotomy during the same period. RESULTS: VATS lobectomy took a longer time than thoracotomy (P < 0.001), but removal of thoracic drainage and patient discharge were earlier for patients in the VATS group (P < 0.001). There was no difference in lymph node dissection, mortality and morbidity between the two groups (P > 0.05). The median follow-up time for 287 patients (89.7%) was 37.0 months (range: 7.0-69.0). The VATS group had a longer survival time than for the thoracotomy group (median 49.0 months vs. 31.7 months, P < 0.001). The increased survival time of the VATS group was due to patients with a single station of N2 metastasis (P = 0.001), rather than to patients with multiple stations of N2 metastasis (P = 0.225). CONCLUSIONS: It is both feasible and safe to perform VATS lobectomy on patients with unexpected N2 NSCLC. VATS provides better survival rates for those patients with just one station of metastatic mediastinal lymph nodes.

MiR-138 inhibits tumor growth through repression of EZH2 in non-small cell lung cancer.

BACKGROUND/AIMS: MicroRNAs (miRNAs) play important roles in tumorigenesis. We investigated the roles and mechanisms of miR-138 in human non-small cell lung cancer (NSCLC). METHODS: The expression of miR-138 was first examined in NSCLC cell lines and tumour tissues by real-time PCR The in vitro and in vivo functional effect of miR-138 was examined further. A luciferase reporter assay was conducted to confirm target association between miR-138 and the enhancer of zeste homolog 2 (EZH2). RESULTS: miR-138 was frequently downregulated in NSCLC cells and tissues. Overexpression of miR-138 inhibited proliferation of NSCLC cells in vitro and tumor growth in vivo. The EZH2 oncogene, which is often overexpressed in various human cancers and acts as an important regulator of cell growth and tumor invasion, was identified as a novel target of miR-138. miR-138 can bind to the 3' untranslated region (3' UTR) of EZH2 and suppress the expression of EZH2 at both mRNA and protein levels. Furthermore, knockdown of EZH2 phenocopied the tumor suppressive effects of miR-138 in cell models, whereas ectopic expression of EZH2 rescued the suppressive effects of miR-138. CONCLUSION: These findings define a tumor suppressor function for miR-138 in NSCLC and further suggest that miR-138 may represent a potential therapeutic target for NSCLC patients.

Video-assisted thoracic surgery lobectomy for unexpected pathologic N2 non-small cell lung cancer.

BACKGROUND: This study was performed to assess early and late outcomes of pathologic N2 disease unexpectedly detected in patients with non-small cell lung cancer undergoing video-assisted thoracic surgery (VATS) lobectomy for clinical stage I. METHODS: We retrospectively reviewed the clinical features of patients with unexpected N2 non-small cell lung cancer and their early and late outcomes in the VATS lobectomy group versus the open thoracotomy lobectomy group. RESULTS: The overall survival time for all 358 patients was 33.26 ± 0.90 months. The overall survival time for 117 cases in the VATS lobectomy group was 36.02 ± 1.44 months. The overall survival time for 241 cases in the open thoracotomy lobectomy group was 31.92 ± 1.14 months. The survival rates for patients in the VATS lobectomy group were 92.31%, 36.75%, 5.13% at one, three, and five years, respectively. The survival rates for patients in the open thoracotomy lobectomy group were 92.12%, 21.58%, 2.49% at one, three, and five years, respectively. A significant difference was found between the two groups regarding this factor ( X ̅ 2 = 3.88 , P = 0.049). CONCLUSIONS: VATS lobectomy is feasible and safe to perform on patients with minimal N2 non-small cell lung cancer. Even if lymph node metastasis is unexpectedly detected during surgery, with rigorous preoperative evaluation and systematic lymph node dissection, there is no need to convert to open thoracotomy lobectomy.