LNC01089-LINC00963/miR-1244-5p/IGF1 ceRNA axis might regulate FOXO signaling pathway in breast cancer patients: a biomarker discovery investigation

Abstract

Abstract Background Breast carcinoma (BC) ranks as one of the most prevalent illnesses among women, and a variety of factors, including inherited and environmental factors, can impact its start and progression. A variety of biological biomarkers (measurement of enzymes, hormones, and mRNA and microRNA expression patterns) have been identified for the prediction of poor prognosis and diagnosis of BC. In this study, we tried to analyze the expression patterns of mRNAs and long non-coding RNAs (lncRNAs) and find novel biomarkers for diagnosis and prognosis of BC during a systems biology approach. Methods Microarray analysis was performed to find novel potential BC biomarkers. Using miRWalk, lncRRIsearch, STRING, and Cytoscape, non-coding and protein interaction analysis was utilized and visualized. Pathway enrichment and gene ontology analyses were performed to find accurate biological mechanisms of selected RNAs. The correlation of lncRNA and mRNA expression level with the survival rate of BC patients was shown using GEPIA2. Expression level of miRNA was performed using ENCORI. Using qRT-PCR on 50 tumor samples compared to 50 control samples for validation of bioinformatics expression analyses and understanding of diagnosis capability of selected RNAs (using Receiver operating characteristic (ROC) analysis. Results IGF1 expression level had a significant reduction in BC, based on microarray and qRT-PCR experiments. LINC00963 and LNC01089 also have significant decrease in expression level, based on GEPIA2 and qRT-PCR. LNC01089 and LINC00963 could represent suitable BC diagnostic (depending on ROC analysis) and prognosis (clinicopathological analysis) biomarkers. The two mentioned lncRNAs have direct interaction with IGF1 mRNA. miR-1244-5p as a potential up-regulated oncogene of BC suppresses the expression level of LNC01089, LINC00963, and IGF1. IGF1 is a key modulator of the FOXO signaling pathway. The mentioned RNAs have a significant correlation with clinicopathological features of BC patients, including age, lymph node metastasis, and menopausal status. Conclusion LINC00963 and LNC01089, as the two potential tumor suppressors of BC, could regulate the FOXO signaling pathway through direct interaction with IGF1 mRNA. miR-1244-5p also might have a critical role in FOXO regulation through suppression of IGF1 and two mentioned lncRNAs.