Dataset Information

Identification of key genes and long non?coding RNAs in celecoxib?treated lung squamous cell carcinoma cell line by RNA?sequencing.

ABSTRACT: Celecoxib is an inhibitor of cyclooxygenase-2, a gene that is often aberrantly expressed in the lung squamous cell carcinoma (LSQCC). The present study aims to provide novel insight into chemoprevention by celecoxib treatment. The human LSQCC cell line SK?MES?1 was treated with or without celecoxib and RNA?sequencing (RNA?seq) was performed on the Illumina HiSeq 2000 platform. Expression levels of genes or long non?coding RNAs (lncRNAs) were calculated by Cufflinks software. Subsequently, differentially expressed genes (DEGs) and differentially expressed lncRNAs (DE?LNRs) between the two groups were selected using the limma package and LNCipedia 3.0, respectively; followed by co?expression analysis based on their expression correlation coefficient (CC). Enrichment analysis for the DEGs and co?expressed DE?LNRs were performed. Protein?protein interaction (PPI) network analysis for DEGs was performed using STRING database. A set of 317 DEGs and 25 DE?LNRs were identified between celecoxib?treated and non?treated cell lines. A total of 12 pathways were enriched by the DEGs, including 'protein processing in endoplasmic reticulum' for activating transcription factor 4 (ATF4), 'mammalian target of rapamycin (mTOR) signaling pathway' for vascular endothelial growth factor A (VEGFA) and 'ECM?receptor interaction' for fibronectin 1 (FN1). Genes such as VEGFA, ATF4 and FN1 were highlighted in the PPI network. VEGFA was linked with lnc?AP000769.1?2:10 (CC= ?0.99227), whereas ATF4 and FN1 were closely correlated with lnc?HFE2?2:1 (CC=0.996159 and ?0.98714, respectively). lncRNAs were also enriched in pathways such as 'mTOR signaling pathway' for lnc?HFE2?2:1. Several important molecules were identified in celecoxib?treated LSQCC cell lines, such as VEGFA, ATF4, FN1, lnc?AP000769.1?2:10 and lnc?HFE2?2:1, which may enhance the anti?cancer effects of celecoxib on LSQCC.

SUBMITTER: Li G

PROVIDER: S-EPMC5928627 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Identification of key genes and long non‑coding RNAs in celecoxib‑treated lung squamous cell carcinoma cell line by RNA‑sequencing.

Li Gang G Wang Xuehai X Luo Qingsong Q Gan Chongzhi C

Molecular medicine reports 20180301 5

Celecoxib is an inhibitor of cyclooxygenase-2, a gene that is often aberrantly expressed in the lung squamous cell carcinoma (LSQCC). The present study aims to provide novel insight into chemoprevention by celecoxib treatment. The human LSQCC cell line SK‑MES‑1 was treated with or without celecoxib and RNA‑sequencing (RNA‑seq) was performed on the Illumina HiSeq 2000 platform. Expression levels of genes or long non‑coding RNAs (lncRNAs) were calculated by Cufflinks software. Subsequently, differ ...[more]

PMID: 29512696

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Project description:BackgroundGene profiling of diffuse large B cell lymphoma (DLBCL) has revealed broad gene expression deregulation compared to normal B cells. While many studies have interrogated well known and annotated genes in DLBCL, none have yet performed a systematic analysis to uncover novel unannotated long non-coding RNAs (lncRNA) in DLBCL. In this study we sought to uncover these lncRNAs by examining RNA-seq data from primary DLBCL tumors and performed supporting analysis to identify potential role of these lncRNAs in DLBCL.MethodsWe performed a systematic analysis of novel lncRNAs from the poly-adenylated transcriptome of 116 primary DLBCL samples. RNA-seq data were processed using de novo transcript assembly pipeline to discover novel lncRNAs in DLBCL. Systematic functional, mutational, cross-species, and co-expression analyses using numerous bioinformatics tools and statistical analysis were performed to characterize these novel lncRNAs.ResultsWe identified 2,632 novel, multi-exonic lncRNAs expressed in more than one tumor, two-thirds of which are not expressed in normal B cells. Long read single molecule sequencing supports the splicing structure of many of these lncRNAs. More than one-third of novel lncRNAs are differentially expressed between the two major DLBCL subtypes, ABC and GCB. Novel lncRNAs are enriched at DLBCL super-enhancers, with a fraction of them conserved between human and dog lymphomas. We see transposable elements (TE) overlap in the exonic regions; particularly significant in the last exon of the novel lncRNAs suggest potential usage of cryptic TE polyadenylation signals. We identified highly co-expressed protein coding genes for at least 88 % of the novel lncRNAs. Functional enrichment analysis of co-expressed genes predicts a potential function for about half of novel lncRNAs. Finally, systematic structural analysis of candidate point mutations (SNVs) suggests that such mutations frequently stabilize lncRNA structures instead of destabilizing them.ConclusionsDiscovery of these 2,632 novel lncRNAs in DLBCL significantly expands the lymphoma transcriptome and our analysis identifies potential roles of these lncRNAs in lymphomagenesis and/or tumor maintenance. For further studies, these novel lncRNAs also provide an abundant source of new targets for antisense oligonucleotide pharmacology, including shared targets between human and dog lymphomas.

Dataset Information

Identification of key genes and long non?coding RNAs in celecoxib?treated lung squamous cell carcinoma cell line by RNA?sequencing.

Publications

Identification of key genes and long non‑coding RNAs in celecoxib‑treated lung squamous cell carcinoma cell line by RNA‑sequencing.

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