Analysis of lncRNA-associated ceRNA network in breast cancer: A new insight into the role of GBP1P1 pseudogene in breast cancer

Background: Pseudogenes are a type of long noncoding RNAs (lncRNA) demonstrated to have a remarkable ability in post-transcriptional regulation, including cancer. Pseudogenes regulate parental gene expression via the competing endogenous RNA (ceRNA) mechanism. In this study, we present an lncRNA ceRNA network in breast cancer. Methods: 378 samples from 10 GEO databases were used to search for significant differentially expressed genes and lncRNAs. Following, the results were confirmed in the TCGA breast cancer database. The experimentally validated miRNAs that target genes and lncRNAs were explored in the DIANA tool to construct a ceRNA network. Finally, the result of ceRNA network analysis was validated in 40 breast cancer patients in lab experiments. Results: We have found 962 genes and lncRNAs in breast cancer. A ceRNA network with the topmost correlated gene-lncRNA and 73 common miRNAs was constructed. Several cancer-related pathways were deregulated, including AKT/mTOR and mTORC1-mediated pathways. We have found three genes with pseudogene pairs with the highest correlations, including GBP1-GBP1P1 , PDE4DIP- PDE4DIPP2 , and CD24-CD24P4 . The GBP1-GBP1P1 had the best correlation with age, menopause status, nodal metastasis, stage, and subclass of patients. Then we assessed the expression of GBP1 and GBP1P1 in 40 breast cancer patients. The expression levels of GBP1 and its pseudogene were significantly upregulated in tumor samples (3.4 and 5.7 fold, respectively). In conclusion, we report a gene-lncRNA ceRNA network in breast cancer that may provide new insights into the role of GBP1P1 in the development of breast cancer.