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.
