Abstract
BackgroundMitochondria-nuclear cross talk and mitochondrial retrograde regulation are involved in the genesis and development of breast cancer (BC). Therefore, mitochondria can be regarded as a promising target for BC therapeutic strategies. In the present study, we aimed to construct regulating network and seek the potential biomarkers of BC diagnosis, prognosis and also the molecular therapeutic targets from the perspective of mitochondrial dysfunction. MethodsThe microarray data of mitochondria-related encoding genes of BC were downloaded from GEO including GSE128610 and GSE72319. GSE128610 was treated as test set and validation sets consisted of GSE72319 and TCGA, which were used for identifying mitochondria-related differential expressed genes (mrDEGs). We performed enrichment analysis, PPI network, hub mrDEGs, and overall survival analysis and constructed transcription factor (TF)-miRNA-hub mrDEGs network. ResultsA total of 23 up-regulated and 71 down-regulated mrDEGs were identified and validated. Enrichment analyses indicated that mrDEGs were associated with several cancer-related biological processes, Moreover, 9 hub mrDEGs were identified and validated in tissues. Finally, 5 hub coregulated mrDEGs, 21 miRNA and 117 TF were used to construct TF-miRNA-hub mrDEGs network. MAZ, HDGF and SP2 could regulate 3 hub mrDEGs. hsa-mir-21-5p, hsa-mir-1-3p, hsa-mir-218-5p, hsa-mir-26a-5p, and hsa-mir-335-5p regulated 2 hub mrDEGs. Overall survival analysis suggested that the up-regulated FN1 and down-regulated DDR2 conferred to poor BC prognosis. ConclusionTF-miRNA-hub mrDEGs has instruction significance for the etiology exploration of BC. The identified hub mrDEGs, such as FN1 and DDR2, were likely to regulate mitochondrial function and might be novel biomarkers of BC diagnosis and prognosis as well as the therapeutic targets.