scholarly journals Identification of SRXN1 and KRT6A as Key Genes in Smoking-Related Non-Small-Cell Lung Cancer Through Bioinformatics and Functional Analyses

2022 ◽  
Vol 11 ◽  
Author(s):  
Jiazhen Zhou ◽  
Guanqing Jiang ◽  
Enwu Xu ◽  
Jiaxin Zhou ◽  
Lili Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Quantitative Pcr ◽  
Nude Mice ◽  
Cell Lung Cancer ◽  
Target Genes ◽  
Small Cell ◽  
The Cancer Genome Atlas ◽  
Small Cell Lung ◽  
Roc Curve Analysis

BackgroundLung cancer is the leading cause of cancer-related mortality worldwide. Although cigarette smoking is an established risk factor for lung cancer, few reliable smoking-related biomarkers for non-small-cell lung cancer (NSCLC) are available. An improved understanding of these biomarkers would further the development of new biomarker-targeted therapies and lead to improvements in overall patient survival.MethodsWe performed bioinformatic analysis to screened potential target genes, then quantitative PCR, western, siRNA, CCK-8, flow cytometry, tumorigenicity assays in nude mice were performed to validated the function.ResultsIn this study, we identified 83 smoking-related genes (SRGs) based on an integration analysis of two Gene Expression Omnibus (GEO) datasets, and 27 hub SRGs with potential carcinogenic effects by analyzing a dataset of smokers with NSCLC in The Cancer Genome Atlas (TCGA) database. A survival analysis revealed three genes with potential prognostic value, namely SRXN1, KRT6A and JAKMIP3. A univariate Cox analysis revealed significant associations of elevated SRXN1 and KRT6A expression with prognosis. A receiver operating characteristic (ROC) curve analysis indicated the high diagnostic value of SRXN1 and KRT6A for smoking and cancer. Quantitative PCR and western blotting validated the increased expression of SRXN1 and KRT6A mRNA and protein, respectively, in lung cancer cell lines and NSCLC tissues. In patients with NSCLC, SRXN1 and KRT6A expression was associated with the tumor–node–metastasis (TNM) stage, presence of metastasis, history of smoking and daily smoking consumption. Furthermore, inhibition of SRXN1 or KRT6A suppressed viability and enhanced apoptosis in the A549 human lung carcinoma cell line. Tumorigenicity assays in nude mice confirmed that the siRNA-mediated downregulation of SRXN1 and KRT6A expression inhibited tumor growth in vivo.ConclusionsIn summary, SRXN1 and KRT6A act as oncogenes in NSCLC and might be potential biomarkers of smoking exposure and the early diagnosis and prognosis of NSCLC in smokers, which is vital for lung cancer therapy.

scholarly journals Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer

2020 ◽  
Author(s):  
Zhi-Gang Sun ◽  
Feng Pan ◽  
Jing-Bo Shao ◽  
Qian-Qian Yan ◽  
Lu Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Nude Mice ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Kinesin Superfamily

Abstract Background: Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cell lung cancer (NSCLC). Methods: KIF21B expression in 72 cases of NSCLC tissues was measured by immunohistochemical staining (IHC). We used shRNA-KIF21B interference to silence KIF21B in NSCLC H1299 and A549 cells and normal lung epithelial bronchus BEAS-2B cells. The biological roles of KIF21B in the growth and metastasis abilities of NSCLC cells were measured by Cell Counting Kit-8 (CCK8), colony formation and Hoechst 33342/PI, wound-healing, and Transwell assays, respectively. Expression of apoptosis-related proteins was determined using western blot. The effect of KIF21B on tumor growth in vivo was examined using nude mice model. Results: KIF21B was up-regulated in NSCLC tissues, and correlated with pathological lymph node and pTNM stage, its high expression was predicted a poor prognosis of patients with NSCLC. Silencing of KIF21B mediated by lentivirus-delivered shRNA significantly inhibited the proliferation ability of H1299 and A549 cells. KIF21B knockdown increased apoptosis in H1299 and A549 cells, down-regulated the expression of Bcl-2 and up-regulated the expression of Bax and active Caspase 3. Moreover, KIF21B knockdown decreased the level of phosphorylated form of Akt (p-Akt) and Cyclin D1 expression in H1299 and A549 cells. In addition, silencing of KIF21B impeded the migration and invasion of H1299 and A549 cells. Further, silencing of KIF 21B dramatically inhibited xenograft growth in BALB/c nude mice. However, silencing of KIF21B did not affect the proliferation, migration and invasion of BEAS-2B cells.Conclusions: These results reveal that KIF21B is up-regulated in NSCLC and acts as an oncogene in the growth and metastasis of NSCLC, which may function as a potential therapeutic target and a prognostic biomarker for NSCLC.

Chronopharmacokinetics and mechanisms of gefitinib in a nude mice model of non-small cell lung cancer

RSC Advances ◽  
2016 ◽  
Vol 6 (98) ◽  
pp. 95780-95788 ◽  
Author(s):  
Le Wang ◽  
Lujia Li ◽  
Liyan Zhao ◽  
Changjiao Liu ◽  
Jiao Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Circadian Rhythms ◽  
Small Cell Lung Cancer ◽  
Nude Mice ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Mice Model ◽  
Small Cell Lung ◽  
Nude Mice Model

Circadian rhythms may influence the pharmacokinetics of drugs.

Biodistribution and Dosimetry of 177Lu-Labeled [DOTA0,Tyr3]Octreotate in Male Nude Mice with Human Small Cell Lung Cancer

2003 ◽  
Vol 18 (4) ◽  
pp. 593-599 ◽  
Author(s):  
Anneli Schmitt ◽  
Peter Bernhardt ◽  
Ola Nilsson ◽  
Håkan Ahlman ◽  
Lars Kölby ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Nude Mice ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

RORγ agonist LYC-55716, a novel small molecule immunotherapy: Rationale for clinical evaluation in non-small cell lung cancer based on translational and bioinformatic evaluation.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 171-171
Author(s):  
Laura Carter ◽  
Xikui Liu ◽  
Hongxiu Li ◽  
Elizabeth Zawidzka ◽  
Yilin Gao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Formation ◽  
Small Cell ◽  
The Cancer Genome Atlas ◽  
Orphan Receptor ◽  
Small Cell Lung

171 Background: Retinoic acid receptor–related orphan receptor γ (RORγ) agonists modulate immune cell gene expression to enhance effector function and decrease regulatory T cell formation and expression of checkpoint pathways. RORγ agonists have demonstrated antitumor activity in syngeneic tumor models. Translational and bioinformatic assessments were conducted to support inclusion of patients with non–small-cell lung cancer (NSCLC) in a Phase 2a expansion of clinical trial LYC-55716-1001 (NCT02929862). Methods: The Cancer Genome Atlas (TCGA) NSCLC dataset was evaluated for (a) expression of RORγ and RORγ-inducing cytokines and correlation with survival; (b) genes related to RORγ biology, biomarkers of endogenous RORγ agonists; and (c) tumor microenvironment (TME) immune profiles. RORγ expression and the in vitro effects of a RORγ agonist on peripheral blood mononuclear cells (PBMCs) from lung adenocarcinoma (LA) and squamous cell carcinoma (SCC) patients were assessed. Results: In TCGA, 25% of NSCLC tumors expressed moderate/high levels of RORγ, suggesting infiltration of Type 17 cells. There was a statistically significant correlation between high RORγ expression and improved survival in LA patients. Genes that support Type 17 cell formation (IL1B, IL23A, IL6) were expressed in ~50% of tumors. RORγ expression was confirmed in PBMCs isolated from LA and SCC patients. Analysis of TCGA data and patient samples identified low expression of sterol efflux and uptake genes, suggesting low levels of endogenous RORγ agonist in TME. In TCGA, high mutational burden and high expression of immune-related genes were found in NSCLC tumors. RORγ agonist treatment of PBMCs from LA and SCC patients increased IL-17A and IL-26 (LA and SCC) and decreased PD1 (LA). In Phase 1 clinical testing, LYC-55716 has been well tolerated, demonstrating long-term disease stabilization in heavily pretreated patients. Conclusions: Bioinformatic analyses of RORγ expression/biology, correlation with improved survival, plus in vitro findings support inclusion of NSCLC in an ongoing Phase 2 clinical trial of LYC-55716.

scholarly journals Cisplatin-controlled p53 gene therapy for human non-small cell lung cancer xenografts in athymic nude mice via the CArG elements

2005 ◽  
Vol 96 (10) ◽  
pp. 706-712 ◽  
Author(s):  
Wei-dong Wang ◽  
Rong Li ◽  
Zheng-tang Chen ◽  
De-zhi Li ◽  
Yu-zhong Duan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gene Therapy ◽  
Small Cell Lung Cancer ◽  
Nude Mice ◽  
Cell Lung Cancer ◽  
P53 Gene ◽  
Small Cell ◽  
Small Cell Lung ◽  
Athymic Nude Mice

scholarly journals Diagnostic MicroRNA Biomarker Discovery for Non-Small-Cell Lung Cancer Adenocarcinoma by Integrative Bioinformatics Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yang Shao ◽  
Bin Liang ◽  
Fei Long ◽  
Shu-Juan Jiang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Target Genes ◽  
Biomarker Discovery ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Small Cell ◽  
Functional Enrichment ◽  
Small Cell Lung

Lung cancer is the leading cause of cancer death and its incidence is ranked high in men and women worldwide. Non-small-cell lung cancer (NSCLC) adenocarcinoma is one of the most frequent histological subtypes of lung cancer. The aberration profile and the molecular mechanism driving its progression are the key for precision therapy of lung cancer, while the screening of biomarkers is essential to the precision early diagnosis and treatment of the cancer. In this work, we applied a bioinformatics method to analyze the dysregulated interaction network of microRNA-mRNA in NSCLC, based on both the gene expression data and the microRNA-gene regulation network. Considering the properties of the substructure and their biological functions, we identified the putative diagnostic biomarker microRNAs, some of which have been reported on the PubMed citations while the rest, that is, miR-204-5p, miR-567, miR-454-3p, miR-338-3p, and miR-139-5p, were predicted as the putative novel microRNA biomarker for the diagnosis of NSCLC adenocarcinoma. They were further validated by functional enrichment analysis of their target genes. These findings deserve further experimental validations for future clinical application.

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