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ZHX2 Promotes HIF1a Oncogenic Signaling in Triple-Negative Breast Cancer

ABSTRACT: ZHX2 Promotes HIF1a Oncogenic Signaling in Triple-Negative Breast Cancer

PROVIDER: PRJNA732468 | ENA |

REPOSITORIES: ENA

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Project description:Background: This study focuses on the analysis of miRNAs expression data in a cohort of 181 well characterised breast cancer samples composed primarily of triple-negative (ER/PR/HER2-negative) tumours with associated genome-wide DNA and mRNA data, extensive patient follow-up and pathological information. Results: We identified 7 miRNAs with a prognostic role in the triple-negative tumours and an additional 8 prognostic miRNAs when the analysis was extended to the set of all ER-negative cases. miRNAs linked to an unfavourable prognosis were associated with a broad spectrum of motility mechanisms involved in the invasion of stromal tissues, such as cell-adhesion, growth factor-mediated signalling pathways, interaction with the extracellular matrix and cytoskeleton remodelling. When we compared different intrinsic molecular subtypes we found 46 miRNAs that were specifically expressed in one or more intrinsic subtypes. Integrated genomic analyses indicated these miRNAs to be largely influenced by DNA genomic aberrations and to exert a silencing effect on their targets through transcriptional down-regulation. Among others, our analyses highlighted the role of miR17-92 and miR-106b-25, two polycistronic miRNA clusters with known oncogenic functions. We showed that their basal-like specific up-regulation is influenced by increased DNA copy number and contributes to the transcriptional phenotype and the activation of oncogenic pathways in basal-like tumours.Conclusions: This is the first study analysing miRNA, mRNA and DNA data in integration with pathological and clinical information, in a large and well-annotated cohort of triple-negative breast cancers. It provides a conceptual framework, as well as integrative methods and system-level results to elucidate the role of miRNAs as biomarkers and modulators of oncogenic processes in these types of tumours. 181 breast tumour samples were analyzed, extracted from 173 patients. For the great majority of patients (165) only one sample was extracted, while for 8 patients two samples were extracted (biological replicates).

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ZHX2 Promotes HIF1a Oncogenic Signaling in Triple-Negative Breast Cancer

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