scholarly journals Circ_MDM2_000139, Circ_ATF2_001418, Circ_CDC25C_002079, and Circ_BIRC6_001271 Are Involved in the Functions of XAV939 in Non-Small Cell Lung Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Haixiang Yu ◽  
Lei Xu ◽  
Zhengjia Liu ◽  
Bo Guo ◽  
Zhifeng Han ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Regulatory Network ◽  
Family Members ◽  
Enrichment Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Relative Expression

Background. The small molecule inhibitor XAV939 could inhibit the proliferation and promote the apoptosis of non-small cell lung cancer (NSCLC) cells. This study was conducted to identify the key circular RNAs (circRNAs) and microRNAs (miRNAs) in XAV939-treated NSCLC cells. Methods. After grouping, the NCL-H1299 cells in the treatment group were treated by 10 μM XAV939 for 12 h. RNA-sequencing was performed, and then the differentially expressed circRNAs (DE-circRNAs) were analyzed by the edgeR package. Using the clusterprofiler package, enrichment analysis for the hosting genes of the DE-circRNAs was performed. Using Cytoscape software, the miRNA-circRNA regulatory network was built for the disease-associated miRNAs and the DE-circRNAs. The DE-circRNAs that could translate into proteins were predicted using circBank database and IRESfinder tool. Finally, the transcription factor (TF)-circRNA regulatory network was built by Cytoscape software. In addition, A549 and HCC-827 cell treatment with XAV939 were used to verify the relative expression levels of key DE-circRNAs. Results. There were 106 DE-circRNAs (including 61 upregulated circRNAs and 45 downregulated circRNAs) between treatment and control groups. Enrichment analysis for the hosting genes of the DE-circRNAs showed that ATF2 was enriched in the TNF signaling pathway. Disease association analysis indicated that 8 circRNAs (including circ_MDM2_000139, circ_ATF2_001418, circ_CDC25C_002079, and circ_BIRC6_001271) were correlated with NSCLC. In the miRNA-circRNA regulatory network, let-7 family members⟶circ_MDM2_000139, miR-16-5p/miR-134-5p⟶circ_ATF2_001418, miR-133b⟶circ_BIRC6_001271, and miR-221-3p/miR-222-3p⟶circ_CDC25C_002079 regulatory pairs were involved. A total of 47 DE-circRNAs could translate into proteins. Additionally, circ_MDM2_000139 was targeted by the TF POLR2A. The verification test showed that the relative expression levels of circ_MDM2_000139, circ_CDC25C_002079, circ_ATF2_001418, and circ_DICER1_000834 in A549 and HCC-827 cell treatment with XAV939 were downregulated comparing with the control. Conclusions. Let-7 family members and POLR2A targeting circ_MDM2_000139, miR-16-5p/miR-134-5p targeting circ_ATF2_001418, miR-133b targeting circ_BIRC6_001271, and miR-221-3p/miR-222-3p targeting circ_CDC25C_002079 might be related to the mechanism in the treatment of NSCLC by XAV939.

lncRNAs as Potential Targets in Small Cell Lung Cancer: MYC -dependent Regulation

2020 ◽  
Vol 20 (17) ◽  
pp. 2074-2081
Author(s):  
Onur Tokgun ◽  
Pervin E. Tokgun ◽  
Kubilay Inci ◽  
Hakan Akca
Keyword(s):  
Lung Cancer ◽  
Stem Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Therapeutic Strategy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Shrna Vector

Background: Small Cell Lung Cancer (SCLC) is a highly aggressive malignancy. MYC family oncogenes are amplified and overexpressed in 20% of SCLCs, showing that MYC oncogenes and MYC regulated genes are strong candidates as therapeutic targets for SCLC. c-MYC plays a fundamental role in cancer stem cell properties and malignant transformation. Several targets have been identified by the activation/repression of MYC. Deregulated expression levels of lncRNAs have also been observed in many cancers. Objective: The aim of the present study is to investigate the lncRNA profiles which depend on MYC expression levels in SCLC. Methods: Firstly, we constructed lentiviral vectors for MYC overexpression/inhibition. MYC expression is suppressed by lentiviral shRNA vector in MYC amplified H82 and N417 cells, and overexpressed by lentiviral inducible overexpression vector in MYC non-amplified H345 cells. LncRNA cDNA is transcribed from total RNA samples, and 91 lncRNAs are evaluated by qRT-PCR. Results: We observed that N417, H82 and H345 cells require MYC for their growth. Besides, MYC is not only found to regulate the expressions of genes related to invasion, stem cell properties, apoptosis and cell cycle (p21, Bcl2, cyclinD1, Sox2, Aldh1a1, and N-Cadherin), but also found to regulate lncRNAs. With this respect, expressions of AK23948, ANRIL, E2F4AS, GAS5, MEG3, H19, L1PA16, SFMBT2, ZEB2NAT, HOTAIR, Sox2OT, PVT1, and BC200 were observed to be in parallel with MYC expression, whereas expressions of Malat1, PTENP1, Neat1, UCA1, SNHG3, and SNHG6 were inversely correlated. Conclusion: Targeting MYC-regulated genes as a therapeutic strategy can be important for SCLC therapy. This study indicated the importance of identifying MYC-regulated lncRNAs and that these can be utilized to develop a therapeutic strategy for SCLC.

scholarly journals Overexpressed C14orf166 associates with disease progression and poor prognosis in non-small-cell lung cancer

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Yan-Wu Zhou ◽  
Rong Li ◽  
Chao-Jun Duan ◽  
Yang Gao ◽  
Yuan-Da Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Prognostic Significance ◽  
Small Cell ◽  
Mrna Levels ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Normal Tissues

Chromosome 14 ORF 166 (C14orf166), a protein involved in the regulation of RNA transcription and translation, has been reported to possess the potency to promote tumorigenesis; however, the role of C14orf166 in non-small-cell lung cancer (NSCLC) remains unknown. The purpose of the present study was to assess C14orf166 expression and its clinical significance in NSCLC. Immunohistochemical staining, quantitative real-time PCR (qRT-PCR), and Western blotting were used to detect the C14orf166 protein and mRNA expression levels in NSCLC tissues compared with adjacent normal tissues, as well as in NSCLC cells lines compared with normal human bronchial epithelial cells (HBE). Then, the correlations between the C14orf166 expression levels and the clinicopathological features of NSCLC were analyzed. Additionally, the Cox proportional hazard model was used to evaluate the prognostic significance of C14orf166. We found that C14orf166 expression increased in carcinoma tissues compared with their adjacent normal tissues at the protein (P<0.001) and mRNA levels (P<0.001). High expression of C14orf166 was significantly associated with the T stage (P=0.006), lymph node metastasis (P=0.001), advanced TNM stage (P<0.001), and chemotherapy (P<0.001). Moreover, according to the survival analysis, patients with overexpressed C14orf166 were inclined to experience a shorter overall survival and disease-free survival time (P<0.001). Multivariate COX analysis implied that C14orf166 was an independent prognostic biomarker. Taken together, our findings indicate that the overexpression of C14orf166 may contribute to the disease progression of NSCLC, represent a novel prognostic predictor and help high-risk patients make better decisions for subsequent therapy.

Tumor expression levels of CSC markers in resectable non-small cell lung cancer.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 7562-7562 ◽  
Author(s):  
Silvia Calabuig ◽  
Eloisa Jantus-Lewintre ◽  
Rut Lucas ◽  
Rosa Farras ◽  
Marta Usó ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Tumor Expression

Influence of Bcl-2 Family Members on the Cellular Response of Small-Cell Lung Cancer Cell Lines to ABT-737

2007 ◽  
Vol 67 (3) ◽  
pp. 1176-1183 ◽  
Author(s):  
Stephen K. Tahir ◽  
Xiufen Yang ◽  
Mark G. Anderson ◽  
Susan E. Morgan-Lappe ◽  
Aparna V. Sarthy ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Lung Cancer ◽  
Cellular Response ◽  
Family Members ◽  
Small Cell ◽  
Lung Cancer Cell ◽  
Small Cell Lung

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.

scholarly journals A Comparative Study of Mouse Hepatic and Intestinal Gene Expression Profiles under PPARαKnockout by Gene Set Enrichment Analysis

PPAR Research ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Kan He ◽  
Qishan Wang ◽  
Yumei Yang ◽  
Minghui Wang ◽  
Yuchun Pan
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Enrichment Analysis ◽  
Small Cell ◽  
Gene Set Enrichment Analysis ◽  
Small Cell Lung ◽  
Gene Set Enrichment ◽  
Tissue Specific

Gene expression profiling of PPARαhas been used in several studies, but fewer studies went further to identify the tissue-specific pathways or genes involved in PPARαactivation in genome-wide. Here, we employed and applied gene set enrichment analysis to two microarray datasets both PPARαrelated respectively in mouse liver and intestine. We suggested that the regulatory mechanism of PPARαactivation by WY14643 in mouse small intestine is more complicated than in liver due to more involved pathways. Several pathways were cancer-related such as pancreatic cancer and small cell lung cancer, which indicated that PPARαmay have an important role in prevention of cancer development. 12 PPARαdependent pathways and 4 PPARαindependent pathways were identified highly common in both liver and intestine of mice. Most of them were metabolism related, such as fatty acid metabolism, tryptophan metabolism, pyruvate metabolism with regard to PPARαregulation but gluconeogenesis and propanoate metabolism independent of PPARαregulation. Keratan sulfate biosynthesis, the pathway of regulation of actin cytoskeleton, the pathways associated with prostate cancer and small cell lung cancer were not identified as hepatic PPARαindependent but as WY14643 dependent ones in intestinal study. We also provided some novel hepatic tissue-specific marker genes.

scholarly journals Expression, Prognosis and Gene Regulation Network of NFAT Transcription Factors in Non-Small Cell Lung Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Jin Ma ◽  
Rao Du ◽  
Yan Huang ◽  
Wen Zhong ◽  
Huan Gui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Mrna Expression ◽  
Cell Lung Cancer ◽  
Expression Patterns ◽  
Lung Squamous Cell Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Aberrant Expression ◽  
Expression Levels

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The nuclear factor of activated T cells (NFAT) family is implicated in tumorigenesis and progression in various types of cancer. However, little is known about their expression patterns, distinct prognostic values, and potential regulatory networks in NSCLC. In this study, we comprehensively analyzed the distinct expression and prognostic value of NFATs in NSCLC through various large databases, including the Oncomine, UCSC Xena Browser, UALCAN databases, Kaplan–Meier Plotter, cBioPortal, and Enrichr. In lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), NFAT1/2/4/5 mRNA expression levels were significantly decreased and NFAT3 mRNA expression level was significantly increased. The cBioPortal database analysis showed that the mRNA dysregulation was one of the single most important factors for NFAT alteration in LUAD and LUSC and that both LUAD and LUSC cases with the alterations in the mRNA expression of NFATs had significantly better overall survival (OS). High expression levels of NFAT1/2/4/5 were significantly associated with better OS in LUAD, whereas high NFAT3 expression led to a worse OS. Overexpression of NFAT1/2 predicted better OS in LUSC, whereas high NFAT5 expression led to a worse OS. The networks for NFATs and the 50 most frequently altered neighbor genes in LUAD and LUSC were also constructed. NFATs and genes significantly associated with NFAT mRNA expression in LUAD and LUSC were significantly enriched in the cGMP-dependent protein kinase and Wnt signaling pathways. These results showed that the NFAT family members displayed varying degrees of abnormal expressions, suggesting that NFATs may be therapeutic targets for patients with NSCLC. Aberrant expression of NFATs was found to be associated with OS in the patients with NSCLC; among NFATs, NFAT3/4 may be new biomarkers for the prognosis of LUAD. However, further studies are required to validate our findings.

scholarly journals Bioinformatics prediction of differential miRNAs in non-small cell lung cancer

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254854
Author(s):  
Kui Xiao ◽  
Shenggang Liu ◽  
Yijia Xiao ◽  
Yang Wang ◽  
Zhiruo Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Survival Analysis ◽  
Drug Metabolism ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Roc Analysis ◽  
Enrichment Analysis ◽  
Small Cell ◽  
Small Cell Lung

Background Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers. The drug resistance of NSCLC has clinically increased. This study aimed to screen miRNAs associated with NSCLC using bioinformatics analysis. We hope that the screened miRNA can provide a research direction for the subsequent treatment of NSCLC. Methods We screened out the common miRNAs after compared the NSCLC-related genes in the TCGA database and GEO database. Selected miRNA was performed ROC analysis, survival analysis, and enrichment analysis (GO term and KEGG pathway). Results A total of 21 miRNAs were screened in the two databases. And they were all highly expressed in normal and low in cancerous tissues. Hsa-mir-30a was selected by ROC analysis and survival analysis. Enrichment analysis showed that the function of hsa-mir-30a is mainly related to cell cycle regulation and drug metabolism. Conclusion Our study found that hsa-mir-30a was differentially expressed in NSCLC, and it mainly affected NSCLC by regulating the cell cycle and drug metabolism.

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