LINC00520 promotes breast cancer development by low expression as a tumor suppressor and prognostic biomarker by regulating the ESR2 expression level: integrated systems biology bioinformatics and experimental analyses

Abstract

Abstract Background ESR2 can have a remarkable effect on the proliferation and tumorigenesis of breast cancer (BC) as a hub tumor suppressor by regulating the effect of estrogen. The abnormal changes in the expression of the co-expressed lncRNAs can have a regulatory effect on the ESR2 expression and cause BC status. In this research, the expression and correlation of ESR2 and a related lncRNA (LINC00520) were examined through different statistical methods. Method An integrated bioinformatics analysis was performed to obtain a reasonable prediction about the relation of potential biomarkers and design an experiment. Based on the Microarray data analysis, pathway enrichment, GO, and ceRNA interaction analyses, a collection of RNAs was selected for the real-time PCR experiment. Several statistical methods were performed to evaluate the difference in the expressions in the BC samples, correlation of RNAs, and the possibility of being prognostic and diagnostic biomarkers (ROC and clinicopathological analysis). Result It is demonstrated that ESR2 (logFC: -1.842, P. Value < 0.0001) and LINC00520 (logFC: -2.231, P. Value < 0.0001) are the two robust breast cancer potential tumor suppressor in BC population. Likewise, it is demonstrated that the expression of these two RNAs has a significantly positive correlation in tumor samples (r: 0.7, P. Value: 0.0008). ESR2 (AUC: 0.9775, P. Value < 0.0001) and LINC00520 (AUC: 0.8450, P. Value: 0.0002) are the two potential diagnostic biomarkers of BC. Furthermore, expression of LINC00520 has a significant correlation with the stage (stage II) and tumor size (less than 5 cm) in the BC patients. Conclusion It is highly possible that the abnormal changes in the expression of LINC00520 can significantly help BC development by affecting the expression of ESR2 and playing a tumor suppressor role in Isfahan BC population. Furthermore, LINC00520 could be considered as a significant prognostic (clinicopathological analysis) and diagnostic (ROC analysis) biomarkers of BC.