抽象的な

FKBP-related ncRNA-mRNA axis in breast cancer

Hanchu Xiong, Zihan Chen, Linbo Wang, Xiao-Fang Yu, Jichun Zhou

Background: Breast cancer (BC) is a disease with morbidity ranking the first of women world widely. FK506-binding protein (FKBP) family has been demonstrated to possess various functions by interacting with different molecular targets in BC. However, a comprehensive ncRNA-mRNA regulatory axis of FKBP has not yet been reported. Methods: FKBP related miRNAs were obtained from miRWalk database. Then, potential lncRNAs, transcription factors as well as mRNAs of screened differentially expressed miRNAs (DE-miRNAs) were analysed by using LncBase v.2, miRGen v3 and miRWalk database. Additionally, differential expression and prognostic analysis of lncRNAs were evaluated using TANRIC database. Next, GO annotation and KEGG pathway analysis were processed using DAVID database. Protein-Protein Interaction (PPI) network was established and hub genes were identified using STRING database. Finally, differential expression and prognostic analysis of hub genes were further conducted using UALCAN and bc-GenExMiner v4.2 database, respectively. Results: Eleven DE-miRNAs, consisting of four FKBP4 related DE-miRNAs and seven FKBP5 related DE-miRNAs, were screened. 482 predicted lncRNAs were found for DE-miRNAs. Then, expression and prognostic results of nine of top twenty 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. 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. Construction and analysis in PPI network showed that RAB7A was selected as a hub gene with the toppest 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. Conclusions: In current study, we firstly established a predicted FKBP-related ncRNA-mRNA regulatory network, thus exploring a comprehensive interpretation of molecular mechanisms and providing potential clues in seeking novel therapeutics for BC. In the future, much more experiments should be conducted to verify our findings.