Prognosis-related autophagy genes in female lung adenocarcinoma.

ABSTRACT: To screen the prognosis-related autophagy genes of female lung adenocarcinoma by the transcriptome data and clinical data from The Cancer Genome Atlas (TCGA) database.In this study, screen meaningful female lung adenocarcinoma differential genes in TCGA, use univariate Cox proportional regression model to select genes related to prognosis, and establish the best risk model. In this study, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were applied for carrying out bioinformatics analysis of gene function.The gene expression and clinical data of 264 female lung adenocarcinoma patient samples were downloaded from TCGA. Twelve down-regulated genes: NRG3, DLC1, NLRC4, DAPK2, HSPB8, PPP1R15A, FOS, NRG1, PRKCQ, GRID1, MAP1LC3C, GABARAPL1. Up-regulated 15 genes: PARP1, BNIP3, P4HB, ATIC, IKBKE, ITGB4, VMP1, PTK6, EIF4EBP1, GAPDH, ATG9B, ERO1A, TMEM74, CDKN2A, BIRC5. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that these genes were significantly associated with autophagy and mitochondria (animals). Multifactor Cox analysis of autophagy-related genes showed that ITGA6, ERO1A, FKBP1A, BAK1, CCR2, FADD, EDEM1, ATG10, ATG4A, DLC1, VAMP7, ST13 were identified as independent prognostic indicators. According to the multivariate Cox proportional hazard regression model, there was a significant difference in the survival rate observed between the high-risk group (n = 124) and the low-risk group (n = 126) during the 10-year follow-up (P < .05). Univariate Cox analysis showed that tumor stage, T, M, and N stages, and risk score were all related to the survival rate of female lung adenocarcinoma patients. Multivariate Cox analysis found that autophagy-related risk scores were independent predictors, with an area under curve (AUC) value of 0.842. At last, there is autophagy genes differentially expressed among various clinicopathological parameters: ATG4A, BAK1, CCR2, DLC1, ERO1A, FKBP1A, ITGA6.The risk score can be used as an independent prognostic indicator for female patients with lung adenocarcinoma. The autophagy genes ITGA6, ERO1A, FKBP1A, BAK1, CCR2, FADD, EDEM1, ATG10, ATG4A, DLC1, VAMP7, ST13 were identified as prognostic genes in female lung adenocarcinoma, which may be the targets of treatment in the future.

Circ_0001421 facilitates glycolysis and lung cancer development by regulating miR-4677-3p/CDCA3.

BACKGROUND: Lung cancer (LC) is a malignant tumor originating in the bronchial mucosa or gland of the lung. Circular RNAs (circRNAs) are proved to be key regulators of tumor progression. However, the regulatory effect of circ_0001421 on lung cancer tumorigenesis remains unclear. METHODS: The expression levels of circ_0001421, microRNA-4677-3p (miR-4677-3p) and cell division cycle associated 3 (CDCA3) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Methyl thiazolyl tetrazolium (MTT), Transwell and Tumor formation assays were performed to explore the role of circ_0001421 in LC. Glucose consumption and lactate production were examined by a Glucose assay kit and a Lactic Acid assay kit. Western blot was utilized to examine the protein levels of Hexokinase 2 (HK2) and CDCA3. The interaction between miR-4677-3p and circ_0001421 or CDCA3 was confirmed by dual-luciferase reporter assay. RESULTS: Circ_0001421 was increased in LC tissues and cells, and knockdown of circ_0001421 repressed cell proliferation, migration, invasion and glycolysis in vitro. Meanwhile, circ_0001421 knockdown inhibited LC tumor growth in vivo. Mechanistically, circ_0001421 could bind to miR-4677-3p, and CDCA3 was a target of miR-4677-3p. Rescue assays manifested that silencing miR-4677-3p or CDCA3 overexpression reversed circ_0001421 knockdown-mediated suppression on cell proliferation, migration, invasion and glycolysis in LC cells. CONCLUSION: Circ_0001421 promoted cell proliferation, migration, invasion and glycolysis in LC by regulating the miR-4677-3p/CDCA3 axis, which providing a new mechanism for LC tumor progression.

Comparison of the efficacy of four endobronchial ablation techniques in dogs.

The present study aimed to evaluate the safety and efficacy of four commonly used ablation techniques, namely neodymium-doped yttrium aluminium garnet (Nd:YAG) laser therapy, argon plasma coagulation (APC), high-frequency electrocautery and CO2 cryotherapy. The techniques were performed at various powers or impedance settings, and for various durations, on the trachea of beagle dogs. Pathological changes of the tracheal wall were assessed by bronchoscopy. The endoscopic gross appearance of lesions induced by ablation treatments was consistent with the histopathological changes. The results suggested that cryotherapy was relatively safe, whereas APC induced superficial tissue coagulative necrosis. Furthermore, Nd:YAG laser therapy was the most efficient technique and showed the greatest penetration potential. In general, tissue injury was exacerbated with extended application time, at constant power or impedance. The safest application parameters were 20 W for ≤1 sec for Nd:YAG laser therapy, 40 W for ≤3 sec for electrocautery, 40 W for ≤5 sec for APC and 100 Ω for ≤120 sec for cryotherapy. At the maximum times, these settings resulted in identical pathological changes. Healing of the lesions following ablation was achieved within 3 weeks. The Nd:YAG laser, APC, electrocautery and cryotherapy endobronchial ablation techniques differed according to their potential and limitations for application on the trachea. However, when applied at specific combinations of power or impedance and duration, they exhibited similar efficacies.

Apoptosis of Lewis Lung Carcinoma Cells Induced by Microwave via p53 and Proapoptotic Proteins In vivo.

BACKGROUND: Microwave therapy is a minimal invasive procedure and has been employed in clinical practice for the treatment of various types of cancers. However, its therapeutic application in non-small-cell lung cancer and the underlying mechanism remains to be investigated. This study aimed to investigate its effect on Lewis lung carcinoma (LLC) tumor in vivo. METHODS: Fifty LLC tumor-bearing C57BL/6 mice were adopted to assess the effect of microwave radiation on the growth and apoptosis of LLC tumor in vivo. These mice were randomly assigned to 10 groups with 5 mice in each group. Five groups were treated by single pulse microwave at different doses for different time, and the other five groups were radiated by multiple-pulse treatment of a single dose. Apoptosis of cancer cells was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Western blotting was applied to detect the expression of proteins. RESULTS: Single pulse of microwave radiation for 5 min had little effect on the mice. Only 15-min microwave radiation at 30 mW/cm2 significantly increased the mice body temperature (2.20 ± 0.82)°C as compared with the other groups (0.78 ± 0.29 °C, 1.24 ± 0.52 °C, 0.78 ± 0.42 °C, respectively), but it did not affect the apoptosis of LLC tumor cells significantly. Continous microwave radiation exposure, single dose microwave radiation once per day for up to seven days, inhibited cell division and induced apoptosis of LLC tumor cells in a dose- and duration-dependent manner. It upregulated the protein levels of p53, Caspase 3, Bax and downregulated Bcl-2 protein. CONCLUSIONS: Multiple exposures of LLC-bearing mice to microwave radiation effectively induced tumor cell apoptosis at least partly by upregulating proapoptotic proteins and downregulating antiapoptotic proteins. Continuous radiation at low microwave intensity for a short time per day is promising in treating non-small-cell lung cancer.

Functional Role of FcγRIIB in the Regulation of Mesenchymal Stem Cell Function.

Mesenchymal stem cells (MSCs) derived from bone marrow are plural-potent stem cells with immune regulatory functions. We aimed to evaluate role of FcγRIIB in the regulation of bone marrow-derived MSC function. MSCs were prepared from mouse bone marrow derived from wild-type (WT) or FcγRIIB-deficient (FcγRIIB-/-) mice. MSCs were co-cultured with bone marrow-derived dendritic cells (BMDCs), and BMDC maturation and function were evaluated by flow cytometric analysis and carboxyfluorescein succinimidyl ester-labeled OT-II T-cell addition. An acute asthma model was established by aeresol ovalbumin challenge in mice. Mice received WT or FcγRIIB-/- MSC therapy. Lung function was evaluated by histological examination and cytokine production measurement. mRNA and protein expression levels of target genes were examined by real-time quantitative polymerase chain reactionor western blotting. We found that MSCs derived from bone marrow exhibit a high level of FcγRIIB expression. FcγRIIB deficiency impaired the suppressive function of MSCs, as FcγRIIB deficiency efficiently reversed the inhibitory effect of MSCs on BMDC maturation and function. Additionally, FcγRIIB-/-MSCs were less potent at suppressing asthma in model mice, possibly through reduced expression of Smad2, Smad3, Cox-2, and prostaglandin E2 in FcγRIIB-/-MSCs. FcγRIIB might play an essential role in regulating the inhibitory effects of MSCs derived from bone marrow.