Mitotically associated long non-coding RNA, MANCR regulates cell cycle in triple negative breast cancer cells

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that is difficult to treat as it is unresponsive to hormone-therapy; therefore, it is imperative to identify novel, targetable regulators of progression in TNBC. Long non-coding RNAs (lncRNAs) are important regulators in breast cancer and have great potential as therapeutic targets; however, little is known about how the majority of lncRNAs function within TNBC cells. In this study, we identify a novel lncRNA, MANCR (LINC00704), which is upregulated in TNBC cells and breast cancer patient samples. Depletion of MANCR in TNBC cells results in a significant decrease in cell proliferation and viability with a concomitant increase in DNA damage. Transcriptome-wide sequencing following MANCR knockdown reveals significant differences in the expression of >2000 genes, and gene set enrichment analysis identifies changes in multiple categories related to cell cycle regulation. Furthermore, MANCR expression is highest in mitotic cells by both RT-qPCR and RNA in situ hybridization. Consistent with a possible role in cell cycle regulation, MANCR-depleted cells have a lower mitotic index and a higher incidence of defective cytokinesis. Taken together, our data reveal a role for the novel lncRNA, MANCR (mitotically-associated long non-coding RNA), in cell cycle regulation of aggressive breast cancer, and identify it as a potential therapeutic target. Transcriptome-wide sequencing following MANCR knockdown