Abstract
Triple negative breast cancer (TNBC) is a highly aggressive breast cancer for which no targeted treatments are available. It commonly metastasises to the brain, bone and lung. Due to the lack of treatment beyond surgery and chemotherapy, early intervention is the best course of action and prognostic tools such as biomarkers are required. Long noncoding RNAs (lncRNAs) are non-protein-coding RNAs longer than 200 nucleotides expressed by cells in a tissue and disease state-specific manner. Circular RNAs (circRNAs) are stable, non-coding RNAs expressed in the same manner. Both have already been used successfully as biomarkers in other cancers, e.g. lncRNA MALAT1 in lung cancer. Thus, we hypothesised that there are lncRNAs and/or circRNAs specific to distant organ-site metastases in TNBC that could be used to predict if and where it is going to metastasise. Four TNBC cell lines were used in this investigation, parental MDA-MB-231 along with its derivatives that metastasise to the lungs, brain, and bone in vivo. Candidate lncRNAs were selected from published data and their expression levels were analysed and compared across these cell lines. A circRNA-seq experiment was also performed to identify significantly upregulated circRNAs in the metastatic cell lines compared to the parental. All selected candidates underwent expression analyses to elucidate differences in expression patterns between primary and metastatic tumours. There were clear expression differences observed between the parental and metastatic cell lines, supporting our hypothesis that there are lncRNAs and circRNAs exported by TNBC cells that could be used as predictive biomarkers for organ site-specific metastasis. Unfortunately, of the candidates analysed, expression differences were not significant enough for use as a selective marker however, further work on alternative candidates could yield promising results.