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RNA-sequencing and microarray data mining revealing: the aberrantly expressed mRNAs were related with a poor outcome in the triple negative breast cancer patients.

ABSTRACT: Background:Triple negative breast cancer (TNBC) account for about 20% of breast carcinomas and the American society of clinical oncology guidelines does not specify approaches for TNBC patients since lack of specific driver molecules and targeted drugs. Methods:We filtered out the aberrantly expressed mRNAs on the basis of RNA-seq data deposited in the Gene Expression Omnibus database, and verified and deeply analyzed screened differentially expressed genes (DEGs) using a combined bioinformatics approach. Results:Of 21,755 genes with 472 TNBC cases from 3 independent laboratories, 159 mRNAs were identified as DEGs. To verify our results, we assessed the expression levels of top 8 DEGs in Oncomine database. The hierarchical clustering analysis, functional and pathway enrichment analysis were carried out for all DEGs. The results reveal that N-acetyltransferase 1 (NAT1) is most obvious of expression change's gene. Protein-protein interaction (PPI) network construction of 159 DEGs selected 3 hub genes: desmoglein 3 (DSG3), family with sequence similarity 83 member D (FAM83D) and GATA binding protein 3 (GATA3). For further analysis of the potential role of NAT1 in TNBC, the co-expression profiles of NAT1 in BC were made out, and we found that there are 5 genes [GATA3, trefoil factor 3 (TFF3), forkhead box A1 (FOXA1), signal peptide, CUB domain and EGF like domain containing 2 (SCUBE2), G protein-coupled receptor 160 (GPR160)] which co-expressed with NAT1 also were DEGs that we screened out before. Co-occurrence analysis confirmed that same as DEGs, GATA3 and SCUBE2 co-expressed with NAT1, and had a tendency towards a co-occurrence with NAT1 in TNBC. The survival curves showed that NAT1, GATA3 and SCUBE2 expression are significantly related with prognosis. Conclusions:From all above results, we speculate that NAT1, GATA3 and SCUBE2 play a vital role in TNBC.

SUBMITTER: Fei H

PROVIDER: S-EPMC7186670 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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RNA-sequencing and microarray data mining revealing: the aberrantly expressed mRNAs were related with a poor outcome in the triple negative breast cancer patients.

Fei Hongjun H Chen Songchang S Xu Chenming C

Annals of translational medicine 20200301 6

<h4>Background</h4>Triple negative breast cancer (TNBC) account for about 20% of breast carcinomas and the American society of clinical oncology guidelines does not specify approaches for TNBC patients since lack of specific driver molecules and targeted drugs.<h4>Methods</h4>We filtered out the aberrantly expressed mRNAs on the basis of RNA-seq data deposited in the Gene Expression Omnibus database, and verified and deeply analyzed screened differentially expressed genes (DEGs) using a combined ...[more]

PMID: 32355807

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Project description:A hypertrophic scar is the result of abnormal repair of the body after trauma. Histopathologically, it is mostly the result of the excessive proliferation of fibroblasts and the accumulation of extracellular matrix. Accumulating evidence has demonstrated that long non?coding RNAs (lncRNAs) have a critical role in the regulation of gene expression and in the pathogenesis of diseases. However, the roles of lncRNAs in hypertrophic scars have remained elusive. The present study investigated the profiles of differentially expressed lncRNAs between fibroblasts derived from a hypertrophic scar and normal skin, and explored the possible mechanisms underlying the development of hypertrophic scars. Microarray data indicated that 6,104 lncRNAs and 2,952 mRNAs were differentially expressed. A set of differentially expressed transcripts as confirmed by reverse transcription?quantitative polymerase chain reaction. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to determine the principal functions of the significantly deregulated genes. Furthermore, associated expression networks, including subgroup analysis, competing endogenous RNAs (ceRNAs) and coding?noncoding co?expression networks were constructed using bioinformatics methods. The homology between differentially expressed lncRNAs and mRNAs was assessed and two exon lncRNA were selected to explore their regulatory mechanisms. The ceRNA network inferred that NR_125715 acted as a competing endogenous RNA, bound to microRNA (miR)?141?3p, miR?200a?3p and miR?29 to regulate the expression of the miRs' targets, including transforming growth factor ?2 (TGFB2). Similarly, NR_046402 acted as a competing endogenous RNA, which bound to miR?133a?3p.1 and miR?4469 to then regulate the expression of the miRs' targets, including DNA polymerase ?1, catalytic subunit (POLD1). In addition, co?expression analysis indicated that the expression of lncRNAs NR_125715 and NR_046402 was correlated with that of TGFB2 and POLD1 mRNA. The identification of these differentially expressed lncRNAs in the hypertrophic scar?derived fibroblasts in the present study, may provide novel insight into the functional interactions of lncRNA, miRNA and mRNA, and lead to novel theories for the pathogenesis and treatment of hypertrophic scars.

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RNA-sequencing and microarray data mining revealing: the aberrantly expressed mRNAs were related with a poor outcome in the triple negative breast cancer patients.

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RNA-sequencing and microarray data mining revealing: the aberrantly expressed mRNAs were related with a poor outcome in the triple negative breast cancer patients.

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