BORG-dependent alterations in the transcriptome of D2.OR cells

The ubiquitous nature of lncRNAs to comprehensively alter cellular transcriptional networks led us to hypothesize that BORG is capable of compelling metastasic, chemoresistant, and pro-survival activities in triple-negative breast cancers by inducing global transcriptomic reprogramming. As such, we performed RNA-seq to garner mechanistic insights into BORG-dependent pathways within D2.OR cells. Accordingly, transcriptional profiles associated with aggressive breast cancers and adaptive survival programs were amongst the top enriched pathways in BORG-expressing D2.OR cells. Most notably, BORG enriched for gene signatures that were critical for the development of chemoresistance towards doxorubicin, as well as a core set of genes upregulated in response to hypoxia, radiotherapy, and serum-deprivation. We performed RNA-seq on parental and BORG-expressing D2.OR organoids propagated in 3D-cultures for 7 days. Sequencing was performed on biological duplicates using Illumina HiSeq 2500 Platform. Two replicate RNA-seq experiments were performed for each condition (total of 4 samples) with an average of ~66 million paired end, 100 nucleotide long reads obtained for each sample.