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Identification of differentially expressed lncRNAs and mRNAs in luminal-B breast cancer by RNA-sequencing

ABSTRACT: Background: Luminal B cancers show much worse outcomes compared to luminal A. This present study aims to screen key lncRNAs and mRNAs correlated with luminal-B breast cancer. Methods: Luminal-B breast cancer tissue samples and adjacent tissue samples were obtained from 4 patients with luminal-B breast cancer. To obtain differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) between luminal-B breast cancer tumor tissues and adjacent tissues, RNA-sequencing and bioinformatics analysis were performed. Functional annotation of DEmRNAs and protein-protein interaction networks (PPI) construction were performed. DEmRNAs transcribed within a 100kb window up- or down-stream of DElncRNAs were searched, which were defined as cis nearby-targeted DEmRNAs of DElncRNAs. DElncRNA-DEmRNA co-expression networks were performed. Results: A total of 1178 DEmRNAs and 273 DElncRNAs between luminal-B breast cancer tumor tissues and adjacent tissues were obtained. Hematopoietic cell lineage, Cytokine-cytokine receptor interaction, Cell adhesion molecules (CAMs) and Primary immunodeficiency were significantly enriched KEGG pathways in luminal-B breast cancer. FN1, EGFR, JAK3, TUBB3 and PTPRC were five hub proteins of the PPI networks. A total of 99 DElncRNAs-nearby-targeted DEmRNA pairs and 1878 DElncRNA-DEmRNA co-expression pairs were obtained. Conclusion: This study determined key genes and lncRNAs involved in luminal-B breast cancer, which expected to present a new avenue for the diagnosis and treatment of luminal-B breast cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE139274 | GEO | 2020/04/14

REPOSITORIES: GEO

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Project description:Adiponectin (APN) is an endogenous adipokine secreted from adipocytes that exerts an anti-inflammation property. AdipoAI is an orally active adiponectin receptor agonist identified by our group, which can emulate APN's anti-inflammatory properties through mechanisms not fully understood. To explore AdipoAI function, we used lncRNA microarray and got differential lncRNA/mRNA expression medicated by AdipoAI. Identified as one kind of non-coding RNA with more than 200bp length, lncRNA has been demonstrated to have abundance biological functions, including anti-inflammatory response. In the current study, we performed an lncRNA microarray in LPS-induced Raw264.7 cells which pre-stimulated with AdipoAI, and screened 110 DElncRNAs and 190 DEmRNAs. Enrichment analyses were conducted to total mRNAs and DEmRNAs, including GSVA, ssGSEA, GO/KEGG, GSEA and PPI analysis. Among all these processes, endocytosis was significantly enriched. A co-expression analysis was built based on DElncRNAs and DEmRNAs. Then, using Targetscan and miRwalk to predict related microRNAs of DElncRNAs and DEmRNAs respectively, we established competing endogenous RNA (ceRNA) networks including 54 mRNAs from 8 GO items. Furthermore, 33 m6A methylation related marker genes were obtained from previous study and used for the construction of m6A related-lncRNA network using the co-expression analysis. We identified FTO as the hub gene of the network, and 14 lncRNAs that interacted with it. The expression levels of 10 lncRNAs selected from ceRNA and FTO- related lncRNAs networks were validated with qRT-PCR. Finally, Macrophage phenotype scores showed that AdipoAI could attenuate the M2b and M2c polarization of macrophage and correlate with the above lncRNAs. Our work reveals that lncRNA might involve in the anti-inflammation process of AdipoAI in LPS-induced macrophages through ceRNA network and epigenetic regulation of m6A. Mechanistically, these lncRNAs associated with AdipoAI might be related to endocytosis and polarization in macrophage, and provide new candidates for the anti-inflammatory application of APN and its receptor agonist.

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Identification of differentially expressed lncRNAs and mRNAs in luminal-B breast cancer by RNA-sequencing

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