EIF4A3-Induced CircDHTKD1 regulates glycolysis in non-small cell lung cancer via stabilizing PFKL.

Lung cancer (LC) is one of the malignancies with the highest incidence and mortality in the world, approximately 85% of which is non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) exert multiple roles in NSCLC occurrence and development. The sequencing results in previous literature have illustrated that multiple circRNAs exhibit upregulation in NSCLC. We attempted to figure out which circRNA exerts an oncogenic role in NSLCL progression. RT-qPCR evaluated circDHTKD1 level in NSCLC tissue specimens and cells. Reverse transcription as well as RNase R digestion assay evaluated circDHTKD1 circular characterization in NSCLC cells. FISH determined circDHTKD1 subcellular distribution in NSCLC cells. Loss- and gain-of-function assays clarified circDHTKD1 role in NSCLC cell growth, tumour growth and glycolysis. Bioinformatics and RIP and RNA pull-down assessed association of circDHTKD1 with upstream molecule Eukaryotic initiation factor 4A-III (EIF4A3) or downstream molecule phosphofructokinase-1 liver type (PFKL) and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) in NSCLC cells. Rescue assays assessed regulatory function of PFKL in circDHTKD1-meidated NSCLC cellular phenotypes. CircDHTKD1 exhibited upregulation and stable circular nature in NSCLC cells. EIF4A3 upregulated circDHTKD1 in NSCLC cells. CircDHTKD1 exerted a promoting influence on NSCLC cell malignant phenotypes and tumour growth. CircDHTKD1 exerted a promoting influence on NSCLC glucose metabolism. CircDHTKD1 exerts a promoting influence on NSCLC glucose metabolism through PFKL upregulation. RIP and RNA pull-down showed that circDHTKD1 could bind to IGF2BP, PFKL could bind to IGF2BP2, and circDHTKD1 promoted the binding of PFKL to IGF2BP2. In addition, RT-qPCR showed that IGF2BP2 knockdown promoted PFKL mRNA degradation, suggesting that IGF2BP2 stabilized PFKL in NSCLC cells. CircDHTKD1 exhibits upregulation in NSCLC. We innovatively validate that EIF4A3-triggered circDHTKD1 upregulation facilitates NSCLC glycolysis through recruiting m6A reader IGF2BP2 to stabilize PFKL, which may provide a new direction for seeking targeted therapy plans of NSCLC.

The roles of long non-coding RNAs in ocular diseases.

In recent years, lncRNAs have been shown to regulate gene expression at the epigenetic, transcriptional and translational level, thus exerting various functions in biological and pathological processes involving cell proliferation, apoptosis, cell cycle and immune response. An increasing number of researches have unveiled that lncRNAs are dysregulated in pathogenesis and the development of different ocular diseases, such as glaucoma, cataract, retinal disease and ocular tumors. Also, it has been reported that lncRNAs may exert significant roles in various ocular diseases. Here, we summarized the functions of lncRNAs on relevant ocular diseases and further clarified their mechanisms. Here, several previous studies with detailed information of lncRNAs which have been proved to be the diagnostic or prognostic biomarkers and potential therapeutic targets were included. Also, it is our hope to provide a thorough knowledge of the functions of lncRNAs in eye diseases and the methods by which lncRNAs can influence ocular diseases.

Survival after lobectomy versus sub-lobar resection in elderly with stage I NSCLC: a meta-analysis.

BACKGROUND: We present a critical comparison of lobectomy and sub-lobar resection in elderly patients with early stage non-small cell lung cancer using meta-analytical techniques. METHODS: A literature search was conducted between the period of December 1997 to March 2019 to identify the comparative studies evaluating 1-, 3-, and 5-year survival rates. The pooled odds ratios (OR) and the 95% confidence intervals (95% CI) were calculated with either the fixed or random effect models, respectively. RESULTS: Six retrospective studies are included in our meta-analysis for a total of 1205 patients. 843 of the individuals were treated with lobectomy, while 362 were treated with sub-lobar resection. We found no significant difference between the lobectomy and the sub-lobar resection in either of the 1-, 3-, or 5-year survival rates. CONCLUSIONS: This study suggests that in elderly individuals with stage I NSCLC, a sub-lobar resection is statistically equivalent to the lobectomy in terms of 1-, 3-, and 5-year survival rates. Further large-scale randomized studies are needed to confirm our results.

PIWIL2 promotes progression of non-small cell lung cancer by inducing CDK2 and Cyclin A expression.

BACKGROUND: PIWI proteins have important roles in tumorigenesis due to their interaction with piRNAs. Recent studies suggest that PIWI proteins affect prognosis of various cancers. METHODS: In the present study, PIWI genes expression was assayed in non-small cell lung cancer (NSCLC). To determine the effects of PIWIL2 on NSCLC cells, overexpression and interference assays were performed using the A549 and H460 cell lines. The tumor formation model was performed to demonstrate the effects of PIWIL2 on tumor formation in vivo. RESULTS: PIWIL2 was increased both at the RNA and protein level in malignant cancer tissues compared with adjacent normal tissue. Moreover, increased PIWIL2 gene expression was negatively correlated with prognosis in NSCLC patients. Overexpression and interference of PIWIL2 promoted and depressed cell proliferation, respectively. Meanwhile, PIWIL2 interference arrested cells at the G2/M stage. In addition, we found that CDK2 and Cyclin A expression were correlated with PIWIL2 expression. Moreover, transfection of PIWIL2 promoted tumor growth in nude mice. CONCLUSION: Our findings shed light on the function of PIWIL2 in NSCLC and suggest potential prognostic and therapeutic value.

Facile Fabrication of Lilac-Like Multiple Self-Supporting WO3 Nanoneedle Arrays with Cubic/Hexagonal Phase Junctions for Highly Sensitive Ethylene Glycol Gas Sensors.

Metal oxides with nanoarray structures have been demonstrated to be prospective materials for the design of gas sensors with high sensitivity. In this work, the WO3 nanoneedle array structures were synthesized by a one-step hydrothermal method and subsequent calcination. It was demonstrated that the calcination of the sample at 400 °C facilitated the construction of lilac-like multiple self-supporting WO3 arrays, with appropriate c/h-WO3 heterophase junction and highly oriented nanoneedles. Sensors with this structure exhibited the highest sensitivity (2305) to 100 ppm ethylene glycol at 160 °C and outstanding selectivity. The enhanced ethylene glycol gas sensing can be attributed to the abundant transport channels and active sites provided by this unique structure. In addition, the more oxygen adsorption caused by the heterophase junction and the aggregation of reaction medium induced by tip effect are both in favor of the improvement on the gas sensing performance.

Graph-DTI: A New Model for Drug-Target Interaction Prediction Based on Heterogenous Network Graph Embedding.

BACKGROUND: In this study, we aimed to develop a new end-to-end learning model called Graph-Drug-Target Interaction (DTI), which integrates various types of information in the heterogeneous network data, and to explore automatic learning of the topology-maintaining representations of drugs and targets, thereby effectively contributing to the prediction of DTI. Precise predictions of DTI can guide drug discovery and development. Most machine learning algorithms integrate multiple data sources and combine them with common embedding methods. However, the relationship between the drugs and target proteins is not well reported. Although some existing studies have used heterogeneous network graphs for DTI prediction, there are many limitations in the neighborhood information between the nodes in the heterogeneous network graphs. We studied the drug-drug interaction (DDI) and DTI from DrugBank Version 3.0, protein-protein interaction (PPI) from the human protein reference database Release 9, drug structure similarity from Morgan fingerprints of radius 2 and calculated by RDKit, and protein sequence similarity from Smith-Waterman score. METHOD: Our study consists of three major components. First, various drugs and target proteins were integrated, and a heterogeneous network was established based on a series of data sets. Second, the graph neural networks-inspired graph auto-encoding method was used to extract high-order structural information from the heterogeneous networks, thereby revealing the description of nodes (drugs and proteins) and their topological neighbors. Finally, potential DTI prediction was made, and the obtained samples were sent to the classifier for secondary classification. RESULTS: The performance of Graph-DTI and all baseline methods was evaluated using the sums of the area under the precision-recall curve (AUPR) and the area under the receiver operating characteristic curve (AUC). The results indicated that Graph-DTI outperformed the baseline methods in both performance results. CONCLUSION: Compared with other baseline DTI prediction methods, the results showed that Graph-DTI had better prediction performance. Additionally, in this study, we effectively classified drugs corresponding to different targets and vice versa. The above findings showed that Graph-DTI provided a powerful tool for drug research, development, and repositioning. Graph-DTI can serve as a drug development and repositioning tool more effectively than previous studies that did not use heterogeneous network graph embedding.

G-quadruplex is critical to epigenetic activation of the lncRNA HOTAIR in cancer cells.

The cancer-promoting lncRNA HOTAIR has multiple isoforms. Which isoform of HOTAIR accounts for its expression and functions in cancer is unknown. Unlike HOTAIR's canonical intergenic isoform NR_003716 (HOTAIR-C), the novel isoform NR_047517 (HOTAIR-N) forms an overlapping antisense transcription locus with HOXC11. We identified HOTAIR-N as the dominant isoform that regulates the gene expression programs and networks for cell proliferation, survival, and death in cancer cells. The CpG island in the HOTAIR-N promoter was marked with epigenetic markers for active transcription. We identified a G-quadruplex (G4) motif rich region in the HOTAIR-N CpG island. Our findings indicate that G4s in HOTAIR-N CpG island is critical for expression of HOTAIR-N in cancer cells. Disruption of G4 may represent a novel therapeutic approach for cancer. The transcriptomes regulated by HOTAIR-N and Bloom in cancer cells as provided herein are important resources for the exploration of lncRNA, DNA helicases, and G4 in cancer.

Establishment of an effective nursing team against COVID-19-a COVID-19 treatment center experience.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) is a serious infectious respiratory disease widespread worldwide. Nurses are the front-line staff in contact with infected patients and play a key role in treating patients and controlling the epidemic. The purpose of this study was to share our nursing team's experience in the treatment of COVID-19 and provide clinical guidance. METHODS: Detail nursing system arrangement was laid down: (I) reasonable division of ward channel was built; (II) effectively arranged human nursing resources and establishing special groups, including Training group, Critical patients nursing group, Quality control group, Epidemic preventive measures group, and Logistics support group; (III) optimize nursing workflow and establish various rules and regulations; (IV) scientific scheduling and humanized management; (V) pay attention to psychological support and adopt humanized management. The pre-job preparation, treatment results, and medical staff infection number were recorded. RESULTS: Fifty-four intensive care nurses all passed the training with an average score of 99.75±0.13. One patient was dead, and 22 patients were discharged smoothly. The average length of stay was 9.12 days. The medical staff was not infected. CONCLUSIONS: The treatment center was set up and functioning rapidly, safely, and orderly by implementing an emergency management strategy. The goal of a high rescue rate, low mortality, and no medical staff infection was achieved. This nursing system could be applied in COVID-19 patient treatment.

Urban trees in university campus: structure, function, and ecological values.

University campuses usually have more trees and can provide various ecosystem services. However, there are few reports on tree ecosystem services of Chinese university campuses, especially in northern China. This study investigated the trees in the campus of Shenyang Institute of Technology and analyzed its ecological benefits and monetary value through i-Tree Streets. The campus trees contained a total of 5193 trees of 66 species, of which Catalpa ovata G. Don, Acer mono Maxim., Rhus typhina Nutt, and Salix babylonica L. accounted for 59.7% of the total number. The age structure of the trees in the campus was not ideal, with 71.5% of young trees, 24.0% of maturing trees, 4.5% of mature trees, and only 0.04% of old trees. The trees in the campus provided more energy saving benefits ($60,850, $11.7/tree), carbon reduction benefits ($34,318, $6.6/tree) and aesthetic benefits ($30,150, $5.8/tree). The benefits resulted from air pollutant removal ($12,889, $2.5/tree) and rainwater runoff interception ($15,534, $3.0/tree) were smaller. In addition, tree species with more maturing trees and mature trees (i.e., with larger diameter at breast height) and large leaf area in the campus contributed significantly to ecosystem services. Our results can provide suggestions and certain insights for Chinese campus greening managers in tree species selection and tree management.

Astragalus polysaccharides protect renal function and affect the TGF-ß/Smad signaling pathway in streptozotocin-induced diabetic rats.

OBJECTIVES: The objective was to observe the effects of Astragalus polysaccharides on diabetes and on regulation of the TGF-ß/Smad signaling pathway. METHODS: A type 2 diabetic rat model was established with a high-fat diet in combination with low-dose streptozotocin (35 mg/kg). Astragalus polysaccharides were applied as treatment intervention and changes in blood glucose and kidney morphology and function were assessed. RESULTS: Eight weeks after model establishment, kidney weight as a proportion of total weight (KW/TW) in the high-, medium-, and low-dose Astragalus polysaccharide groups was significantly lower than that in the model group, and the KW/TW value gradually decreased with increasing dose of polysaccharides in each treatment group. Fasting blood glucose in the low- and medium-dose Astragalus polysaccharide groups was numerically lower than that in the model group and fasting blood glucose in rats in the high-dose group was significantly lower than that in the model group. Levels of 24-hour urinary microalbumin, creatinine, blood urea nitrogen, collagens I, III, and IV, α-smooth muscle actin, transforming growth factor-ß1, and Smad3 in Astragalus polysaccharide groups (all doses) were significantly lower than those in the model group. CONCLUSIONS: Astragalus polysaccharide significantly improved blood glucose and protected kidney function in a rat diabetes model.

The protective effects of lycopus lucidus turcz in diabetic retinopathy and its possible mechanisms.

The aim of the present study was to investigate the effect of Lycopus lucidus Turcz (LT) on diabetic retinopathy (DR) and its underlying mechanisms. SD rats and human retinal microvascular endothelial cells (HRECs) were applied for establishment DR model. HE and TUNEL staining were used to evaluate the pathological changes and apoptosis of retinal ganglion cells. Additionally, retinal vessels were detected by immunofluorescence staining with CD31 and VEGF. The function of BRB was observed using Evans blue. Moreover, the oxidative stress, inflammation and angiogenesis associated factors were measured respectively. The expression of p38-MAPK/NF-κB signalling proteins were detected by Western blot. The results demonstrated that pathological changes and retinal optic disc cells apoptosis in retinas of diabetic rats, both of which were reduced in the LT-treated group. And LT treatment attenuated the levels of oxidative stress, inflammation and angiogenesis factors. Importantly, the expression levels of p-p38, p-ERK, p-JNK and NF-κB were decreased. After treatment with TNF-α combined with LT, the levels of inflammatory factors were decreased but higher than the negative control. Taken together, the results suggested that LT treatment is of therapeutic benefit by ameliorating oxidative stress, inflammation and angiogenesis of DR via p38-MAPK/NF-κB signaling pathway.

HOX transcript antisense RNA (HOTAIR) in cancer.

Long noncoding RNAs (lncRNAs) have emerged as a new family of master regulators of cancer. The lncRNA HOX transcript antisense RNA (HOTAIR) is a prime example of an oncogenic trans-acting lncRNA. The expression of HOTAIR is elevated in a broad spectrum of cancers and is associated with metastasis and poor prognosis. HOTAIR governs fundamental biochemical and cellular processes via interactions with a variety of partners to promote proliferation, invasion, survival, drug resistance, and metastasis in preclinical studies of cancer. Here, we review the diagnostic and therapeutic potential of HOTAIR as well as the molecular mechanisms underlying the dysregulation of its expression and function in cancer. We also discuss the challenges to capitalizing on HOTAIR for more effective patient care along with future directions founded on the recent exciting advances in our knowledge of HOTAIR in cancer.

RUFY3 Predicts Poor Prognosis and Promotes Metastasis through Epithelial-mesenchymal Transition in Lung Adenocarcinoma.

Background: RUFY3 (RUN and FYVE domain-containing protein 3) has been shown to participate in cell migration, membrane transportation, and cellular signaling and is dysregulated in several cancer processes. However, the role of RUFY3 in lung cancer remains unclear. In the present study, we aimed to study the expression of RUFY3 and assess its clinical significance in lung adenocarcinoma. Materials and Methods: We used immunohistochemistry to detect RUFY3 protein expression in human lung adenocarcinoma and adjacent normal lung tissue from 125 patients who underwent surgical resection of the lung cancer. RUFY3 expression was assessed in association with clinicopathological characteristics and clinical prognosis of lung adenocarcinoma patients. The expression of RUFY3 in three different lung adenocarcinoma cell lines and one normal lung epithelial cell (BEAS-2B) was detected by western blot. RNAi technique was used to silence RUFY3. We assessed cell migration by Trans-well assay and wound healing assay. Results: In lung adenocarcinoma tissues, RUFY3 protein was significantly upregulated compared to paired normal lung tissues. High cytoplasmic RUFY3 levels were associated with lymph node metastasis, TNM staging, and survival status. Patients with the highest expression level of RUFY3 had a shorter survival time than patients with the lowest expression. Inhibition of RUFY3 by siRNA inhibited cell migration. Furthermore, silence of RUFY3 lead to up-regulation of E-cadherin, but down-regulation of N-cadherin, Vimentin and Slug. Conclusions: Our study is first to demonstrated that abnormal expression of RUFY3 indicates poor prognosis in lung adenocarcinoma and also indicates that RUFY3 may be related to EMT process. This highlights the potential of RUFY3 as a novel prognostic biomarker for lung adenocarcinoma.

RFC3 induces epithelial­mesenchymal transition in lung adenocarcinoma cells through the Wnt/ß­catenin pathway and possesses prognostic value in lung adenocarcinoma.

Lung cancer is a malignant tumor responsible for the highest mortality rate in humans. The identification of novel functional genes is of great importance in the treatment of lung cancer. The reported roles of replication factor C subunit 3 (RFC3) in tumorigenesis are contradictory. The present study aimed to explore the role and mechanism of RFC3 in lung cancer cells. An immunohistochemical study of 165 lung cancer and adjacent tissues was conducted (123 lung adenocarcinoma tissues and 42 lung squamous cell carcinoma tissues). Kaplan­Meier analysis and Cox multivariate analysis were employed to explore the relationship between RFC3 and patient prognosis. In addition, the proliferation, cell cycle distribution and apoptosis of A549 and H1299 cells were determined by MTT assay and flow cytometry, respectively, following cell transfection to induce overexpression and knockdown of RFC3. A Boyden chamber assay and wound­healing assay were conducted to determine the invasive and migratory abilities of A549 and H1299 cells. Western blotting was used to analyze the effects of RFC3 overexpression and RFC3 small interfering RNA­induced knockdown, and to explore the potential mechanism and pathway underlying the effects of RFC3. Positive expression of RFC3 was detected in lung adenocarcinoma, and overexpression of RFC3 shortened the survival time of patients with lung adenocarcinoma. Furthermore, overexpression of RFC3 increased the invasion and migration of A549 cells, whereas knockdown of RFC3 significantly reduced the invasion and migration of H1299 cells. Ectopic expression of RFC3 induced epithelial­mesenchymal transition (EMT), as determined by downregulation of E­cadherin, and upregulation of N­cadherin, vimentin and Wnt signaling target genes, including c­MYC, Wnt1 and ß­catenin, and the ratio of phosphorylated­glycogen synthase kinase 3 (GSK3)­ß (Ser9)/GSK3­ß. In conclusion, RFC3 may be considered a coactivator that promotes the Wnt/ß­catenin signaling pathway, and induces EMT and metastasis in lung adenocarcinoma.

Clinical significance of Wip1 overexpression and its association with the p38MAPK/p53/p16 pathway in NSCLC.

Wip1 is deregulated in numerous human malignancies. However, its roles in non­small cell lung cancer (NSCLC) remain unclear. In the current study, the expression of Wip1 was investigated in NSCLC and its clinical significance was detected. Immunohistochemical staining was used to measure the expression of (wild­type p53 induced phosphatase 1) Wip1, p38 mitogen­activated protein kinase (MAPK), p53, p16 protein in a group of 60 NSCLC and 20 normal lung tissues. In addition, western blotting was performed to detect the Wip1 protein in fresh tissues. The correlations between clinical characteristics and Wip1 expression were analyzed using SPSS, version 16.0 software. The expression of Wip1 was positive in 63.3% (38/60) of NSCLC tissues, and in none of the normal lung tissues (0/20; P<0.01). In addition, Wip1 overexpression was significantly associated with tumor length and differentiation (P=0.008 and 0.03, respectively). The expression of Wip1 was negatively correlated with that of p38MAPK, p53 and p16 (r=­0.284, ­0.352 and ­0.348, respectively). The results of the current study demonstrated that Wip1 was frequently overexpressed in NSCLC, which may serve an essential role in the p38MAPK/p53/p16 signaling pathway.

Role of AXL expression in non-small cell lung cancer.

The present study aimed to investigate the expression profile of AXL in non-small cell lung cancer (NSCLC) and its clinical significance. The current study included 257 NSCLC patients, tyrosine-protein kinase receptor UFO (AXL) expression in paired lung cancer and adjacent normal lung tissues of NSCLC patients were compared by immunohistochemistry, western blot analysis and quantitative polymerase chain reaction (qPCR). These methods were used to detect the expression of the AXL gene and protein in fresh tissues from 35 patients. Small interfering RNA (siRNA) was transfected into the H1299 lung cancer cell line to knock down AXL expression; the effects of AXL-siRNA on cell proliferation and migration were examined by MTT and Transwell migration assay, respectively. It was found that AXL staining density in lung cancer tissues was significantly increased compared with adjacent normal lung tissues (55.25 vs. 26.85%; P<0.01); and the expression level of AXL in NSCLC patients was significantly associated with the degree of tumor differentiation (P<0.01) and the clinical stage of disease (P<0.01). Western blotting and qPCR showed that AXL expression was significantly higher in cancer tissues compared with that in adjacent lung tissue (P<0.05). Additionally, the current study also showed that AXL-siRNA inhibited H1299 cell proliferation and migration in vitro. The present study demonstrates the association between increased expression of AXL in NSCLC and the low differentiation phenotype, and its effects on cell proliferation and migration, suggesting its potential clinical values for the prognosis of NSCLC.

Paraneoplastic Cushing's syndrome associated with bronchopulmonary carcinoid tumor in youth: A case report and review of the literature.

Paraneoplastic Cushing's syndrome (CushingPS) caused by bronchopulmonary carcinoid tumors presents a diagnostic challenge for clinicians. The present study reports the case of an 18-year-old male patient presenting with rapid weight gain, polyuria, polydipsia and progressive muscle weakness. Chemical and imaging findings suggested ectopic secretion of adrenocorticotropin. Whole-body 18fluorine-fluorodeoxyglucose (18FDG-PET/CT) positron-emission tomography revealed an increased uptake of 18FDG-PET/CT in the right middle lung mass and lobar lymph node. Postoperative pathology confirmed the presence of a typical carcinoid, as well as a lobar lymph node metastasis. The patient underwent a right middle lobectomy with mediastinal lymph node resection, which resulted in symptom clearance, followed by rapid weight loss. No CushingPS or tumor recurrence was observed at the 3-month postoperative follow-up.

Insights into the roles of hnRNP A2/B1 and AXL in non-small cell lung cancer.

Lung cancer has long been one of the most serious types of malignant tumor, and is associated with high incidence and mortality rates. Despite advancements in the comprehensive treatment of the disease, particularly with targeted therapeutic agents, there has been little improvement in the 5-year survival rates of patients. One of the leading causes of mortality in lung cancer is the lack of effective early diagnostic criteria. On this basis, the present study aimed to identify an index with potential in the early diagnosis and prognosis of lung cancer. The current study determined the expression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 and AXL proteins in non-small cell lung cancer (NSCLC) tumor samples, and performed prognostic analysis of the collected clinical data to identify any association. In addition, RNA interference was performed to silence the expression of hnRNP A2/B1, allowing evaluation of its molecular and cellular functions, and determination of the mechanism of hnRNP A2/B1 in NSCLC by means of AXL mediation. It was identified that the positive expression rate of hnRNP A2/B1 and AXL proteins were significantly higher in NSCLC compared with paracancerous lung tissues (P<0.05). Furthermore, the expression of hnRNP A2/B1 protein was correlated with the expression AXL. Thus, the expression of hnRNP A2/B1 and AXL protein are factors affecting prognosis in patients with NSCLC. Of these, hnRNP A2/B1 appears to be an independent risk factor.

The long non-coding RNA, GAS5, enhances gefitinib-induced cell death in innate EGFR tyrosine kinase inhibitor-resistant lung adenocarcinoma cells with wide-type EGFR via downregulation of the IGF-1R expression.

BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are approved for patients with recurrent non-small cell lung cancer (NSCLC). However, the efficacy of EGFR-TKIs in NSCLC therapy is limited by primary and acquired resistance. Recent studies have revealed that long non-coding RNAs (LncRNA) may be involved in EGFR-TKI resistance. Therefore, a better understanding of the interactive mechanisms underlying LncRNA-mediated EGFR-TKIs resistance may help us to improve clinical response rates. METHOD: To investigate the expression of growth arrest-specific 5 (GAS5) in lung adenocarcinoma, we performed real-time reverse-transcriptase polymerase chain reaction. The correlation between GAS5 expression levels and the samples' clinicopathological features was also analyzed. Primary resistance to EGFR-TKIs was identified in the human lung adenocarcinoma cell line A549. Plasmid vectors were used to overexpress GAS5 in A549 cells. MTT (3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide) colony formation assays and EdU (5-ethynyl-2'-deoxyuridine) assays were used to assess cell proliferation, and flow-cytometric analysis was used to evaluate the apoptosis rate. The expression levels of our target proteins, namely, EGFR, p-EGFR, ERK, p-ERK, Akt, p-Akt, IGF-1R (insulin-like growth factor 1 receptor), and p-IGF-1R, were analyzed by western blotting. A549 cells transfected with pcDNA-GAS5 were injected into nude mice. The transplanted mice were treated with gefitinib to study the effect of GAS5 on the resistance to EGFR-TKIs in vivo. RESULTS: Our results showed that GAS5 was significantly downregulated in lung adenocarcinoma tissues compared with the paired adjacent non-tumorous tissue samples. Furthermore, lower GAS5 expression levels were associated with larger tumor sizes, poor tumor differentiation, and advanced pathological stages. However, GAS5 was almost equally expressed between benign tumors compared with the adjacent normal tissues. GAS5 was also overexpressed in EGFR-TKI sensitive cell lines compared with the resistant cell line. Using MTT, EdU incorporation, and colony formation assays, we showed that GAS5-expressing A549 cells displayed an elevated level of cell death. In addition to its pro-apoptotic effect in the A549 cell line, GAS5 overexpression also suppressed the growth of A549-derived tumors in nude mice treated with gefitinib. GAS5 overexpression was inversely correlated with the expression of the EGFR pathway and IGF-1R proteins. CONCLUSIONS: Collectively, our results indicated that GAS5 LncRNA may represent a potential biomarker for the diagnosis of lung adenocarcinoma and that GAS5 might play a novel role in the development of the resistance to gefitinib, which could be reversed by overexpressing GAS5.

[Detection of Chemerin and It's Clinical Significance in Peripheral Blood of Patients with Lung Cancer.].

BACKGROUND: Chemerin was recently found a chemoattractant just like a chemotatic factor. It can induce immune chemotaxis to dendritic cells and macrophages by binding to its receptor ChemR23. It has been known that the activation of Chemerin could enhance the phagocytosis and antigen presentation of APC. Along with this observation, the contribution of Chemerin in the genesis and development of a tumor attracts more attention. We explored the relation between Chemerin and lung cancer through detecting the expression of Chemerin in peripheral blood of patients. METHODS: The experiment selected samples of lung cancer patients and normal people. The concentration of Chemerin in peripheral blood was detected by ELISA method. T test was used to compare the statistic difference. We compared the concentration of Chemerin in peripheral blood with age, sex, pathological type, degree of differentiation, metastasis of lymphonode, UICC staging and other clinicopathological index, and analyzed by t test and one-way ANOVA. RESULTS: The concentration of Chemerin in peripheral blood of 42 patients with lung cancer (1 965.81 pg/mL+/-374.03 pg/mL) were significantly higher than the concentration of 31 healthy examination (1 111.44 pg/mL+/-250.72 pg/mL)(P<0.001). The concentration of Chemerin in peripheral blood of patients with lung cancer had no relationship with clinicopathological factors. CONCLUSIONS: Chemerin has the potential to lung cancer diagnosis as a marker.