Abstract
Breast cancer leads to most of cancer deaths among women worldwide. Systematically analyzing the competing endogenous RNA (ceRNA) network and their functional modules may provide valuable insight into the pathogenesis of breast cancer. In this study, we constructed a lncRNA-TF-associated ceRNA network via combining all the significant lncRNA-TF ceRNA pairs and TF-TF PPI pairs. We computed important topological features of the network, such as degree and average path length. Hub nodes in the lncRNA-TF-associated ceRNA network were extracted to detect differential expression in different subtypes and tumor stages of breast cancer. MCODE was used for identifying the closely connected modules from the ceRNA network. Survival analysis was further used for evaluating whether the modules had prognosis effects on breast cancer. TF motif searching analysis was performed for investigating the binding potentials between lncRNAs and TFs. As a result, a lncRNA-TF-associated ceRNA network in breast cancer was constructed, which had a scale-free property. Hub nodes such as MDM4, ZNF410, AC0842-19, and CTB-89H12 were differentially expressed between cancer and normal sample in different subtypes and tumor stages. Two closely connected modules were identified to significantly classify patients into a low-risk group and high-risk group with different clinical outcomes. TF motif searching analysis suggested that TFs, such as NFAT5, might bind to the promoter and enhancer regions of hub lncRNAs and function in breast cancer biology. The results demonstrated that the synergistic, competitive lncRNA-TF ceRNA network and their functional modules played important roles in the biological processes and molecular functions of breast cancer.
Highlights
Breast cancer is one of the most common female cancers worldwide, which is the second leading cause of female cancer death [1]
A Long noncoding RNAs (lncRNAs)-Transcription factors (TFs)-associated competing endogenous RNA (ceRNA) network in breast cancer was constructed by combining all significant lncRNA-TF ceRNA pairs and TF-TF protein-protein interactions (PPIs) pairs (Figure 1, details in methods)
These results suggested that hub genes of the lncRNA-TF-associated ceRNA network played important roles in the local region of the network
Summary
Breast cancer is one of the most common female cancers worldwide, which is the second leading cause of female cancer death [1]. Tumor metastasis and drug resistance are still a concern during breast cancer therapy. There is an urgent need to identify key biomarkers and uncover potential molecular mechanisms for breast cancer diagnosis and therapy. Many studies have identified some important genes that participated in the occurrence, development, and metastasis of breast cancer. Two well-known cancer genes, BRCA1 and BRCA2, were the major genes associated with the genetic etiology of breast cancer. Women with BRCA1/BRCA2 mutations had very high risk to develop breast cancer [3]. Mutations or variants of other genes such as TP53, ATM, BARD1, CHECK2, FGFR2, GSTM1, and MAP3K1 have been reported to increase the risk of breast cancer [4]
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