In-Silico Identification and Analysis of lncRNAs and mRNAs in Breast Cancer

Abstract

Long non-coding RNAs (lncRNAs) are the major participants in carcinogenesis. They also regulate important pathways of breast cancer which is one of the major causes of deaths globally. There are four subtypes of breast cancer i.e. luminal- A, luminal-B, HER2 positive and triple-negative and this study includes analysis on all of these subtypes. lncRNAs perform their function by regulating messenger RNA (mRNA) and influence various cellular pathways, gene expression, transcription and post transcriptional regulation. This study is based on the identification of differential expression (DE) patterns and co-expression of lncRNA and mRNA in breast cancer samples taken from microarray and RNA-Seq data, respectively. This study determines the aberrant expression of lncRNAs and their cis- and trans- target mRNA genes that can serve in identification of the novel lncRNA-mRNA interactions in breast cancer. This analysis was performed on 10 samples of lncRNA and 20 samples of mRNA data using statistical R packages. There were 182 differentially expressed and 267 co-expressed lncRNAs obtained from the analysis. DE analysis of mRNA was carried on three subtypes of breast cancer and gave 7113 differentially expressed genes in triple-negative breast cancer (TNBC), 2 in non-TNBC and 16789 in human epidermal growth factor receptor 2 (HER2) positive subtype. The co-expressed mRNA genes were 138 in total. After integrative analysis the results showed novel lncRNA-mRNA interactions of RP11-108F13.2 with TAF5L, RPL23AP2 with CYP4F3, CYP4F8 and AL022324.2 targeting LRP5L, AL022324.3 and Z99916.3 respectively. These interactions were significantly differentially expressed and co-expressed. These aberrantly expressed lncRNAs and their targets could serve as candidate biomarkers as they regulate the major pathways in breast cancer such as metabolic pathways and signaling pathways. Moreover, they can also be used as potential therapeutic targets in future.