Mitotically-Associated lncRNA (MANCR) Affects Genomic Stability and Cell Division in Aggressive Breast Cancer

• Published in: Molecular cancer research 2018-04, Vol.16 (4), p.587-598
• Main Authors: Tracy, Kirsten M, Tye, Coralee E, Ghule, Prachi N, Malaby, Heidi L H, Stumpff, Jason, Stein, Janet L, Stein, Gary S, Lian, Jane B
• Format: Article
• Language: English
• Subjects: Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer; Cell death; Cell division; Cell growth; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cytokinesis; Deoxyribonucleic acid; DNA; DNA damage; DNA sequencing; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene set enrichment analysis; Genomic Instability; Humans; Mitosis; Regulation; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; Sequence Analysis, RNA; Stability; Therapeutic applications; Up-Regulation; Viability
• ISSN: 1541-7786; 1557-3125
• DOI: 10.1158/1541-7786.MCR-17-0548

Aggressive breast cancer is difficult to treat as it is unresponsive to many hormone-based therapies; therefore, it is imperative to identify novel, targetable regulators of progression. Long non-coding RNAs (lncRNA) 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 breast cancer. This study characterizes a novel lncRNA, MANCR (mitotically-associated long noncoding RNA; LINC00704), which is upregulated in breast cancer patient specimens and cells. Depletion of MANCR in triple-negative breast cancer cells significantly decreases cell proliferation and viability, with concomitant increases in DNA damage. Transcriptome analysis, based on RNA sequencing, following MANCR knockdown reveals significant differences in the expression of >2,000 transcripts, 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 hybridization. Consistent with a role in cell-cycle regulation, MANCR-depleted cells have a lower mitotic index and higher incidences of defective cytokinesis and cell death. Taken together, these data reveal a role for the novel lncRNA, MANCR, in genomic stability of aggressive breast cancer, and identify it as a potential therapeutic target. The novel lncRNA, MANCR (LINC00704), is upregulated in breast cancer and is functionally linked with cell proliferation, viability, and genomic stability. .