Construction and analysis of pseudogene-related ceRNA network in breast cancer

Abstract

AbstractBreast cancer (BC) is one of the leading causes of cancer-related deaths in women. The present study explored the potential role of pseudogenes in BC via construction and analysis of a competing endogenous RNA (ceRNA) network through a three-step process. First, we screened differentially expressed genes in nine BC datasets. Then the gene-pseudogenes pairs (nine hub genes) were selected according to the functional enrichment and correlation analysis. Second, the candidate hub genes and interacting miRNAs were used to construct the ceRNA network. Further analysis of the ceRNA network revealed a crucial ceRNA module with two genes-pseudogene pairs and two miRNAs. The in-depth analysis identified the GBP1/hsa-miR-30d-5p/GBP1P1 axis as a potential tumorigenic axis in BC patients. In the third step, the GBP1/hsa-miR-30d-5p/GBP1P1 axis expression level was assessed in 40 tumor/normal BC patients and MCF-7 cell lines. The expression of GBP1 and GBP1P1 was significantly higher in the tumor compared to the normal tissue. However, the expression of hsa-miR-30d-5p was lower in tumor samples. Then, we introduced the GBP1P1 pseudogene into the MCF-7 cell line to evaluate its effect on GBP1 and hsa-miR-30d-5p expression. As expected, the GBP1 level increased while the hsa-miR-30d-5p level decreased in the GBP1P1-overexprsssing cell line. In addition, the oncogenic properties of MCF-7 (cell viability, clonogenicity, and migration) were improved after GBP1P1 overexpression. In conclusion, we report a ceRNA network that may provide new insight into the role of pseudogenes in BC development.