FKBP-related ncRNA-mRNA axis in breast cancer

Hanchu Xiong,Zihan Chen,Weijun Chen,Qiang Li,Baihua Lin,Yongshi Jia

doi:10.1016/j.ygeno.2020.08.017

Hanchu Xiong, Zihan Chen + Show 4 more

Open Access

https://doi.org/10.1016/j.ygeno.2020.08.017

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Abstract

Breast cancer (BC) is a disease with morbidity ranking the first of women worldwidely. In current study, 11 DE-miRNAs, consisting of four FKBP4 related DE-miRNAs and seven FKBP5 related DE-miRNAs, were screened. Four hundred and eighty two predicted lncRNAs were found for DE-miRNAs. Then, expression and prognostic results of nine of top 20 lncRNAs of BC were significantly identified. LINC00662 and LINC00963 expression were significantly associated with patients' overall survival (OS). Then, nine potential upstream transcription factors were identified in motifs of DE-miRNAs. Three hundred and twenty target genes were identified for GO annotation and KEGG pathway analysis, which were mainly enriched in cysteine-type endopeptidase activity involved in apoptotic process. Construction and analysis in PPI network showed that RAB7A was selected as a hub gene with the topest connectivity scores. Differential expression analysis of nine in top ten hub genes of BC were significantly identified. RAB7A and ARRB1 expression were significantly related with BC patients' OS.

Highlights

Breast cancer (BC) is a disease with morbidity ranking the first of women worldwidely
Nine potential upstream transcription factors were identified in motifs of DE-miRNAs. 320 target genes were identified for GO annotation and KEGG pathway analysis, which were mainly enriched in cysteine-type endopeptidase activity involved in apoptotic process
Validation Of Lncrna Differential Expressions And Prognostic Functions. Both expression levels of top twenty long non-coding RNA (lncRNA) in different subtypes and their prognostic roles of overall survival of BC patients were further validated by using The Atlas of ncRNA in Cancer (TANRIC), an open-access database for interactive exploration of lncRNAs of various cancer[11]. lncRNAs with |log2FC|>2 and P < 0.05 were regarded as statistically significant

Summary

Introduction

Breast cancer (BC) is a disease with morbidity ranking the first of women worldwidely. Differential expression and prognostic analysis of hub genes were further conducted using UALCAN and bc-GenExMiner v4.2 database, respectively. Nine potential upstream transcription factors were identified in motifs of DE-miRNAs. 320 target genes were identified for GO annotation and KEGG pathway analysis, which were mainly enriched in cysteine-type endopeptidase activity involved in apoptotic process. Differential expression analysis of nine in top ten hub genes of BC were significantly identified. Conclusions In current study, we firstly established a predicted FKBP-related ncRNA-mRNA regulatory network, exploring a comprehensive interpretation of molecular mechanisms and providing potential clues in seeking novel therapeutics for BC. Despite many researches on miRNA expression and function of BC have been conducted, a comprehensive analysis of FKBP-related ncRNA-mRNA regulatory network via clinical information of BC is still lacking. Construction of predicted ncRNAmRNA axis contributing to BC might unravel the potential molecular mechanisms underlying processes of miRNAs’ impact on BC

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