LncRNA function in a broad range of cellular processes including cell proliferation, apoptosis, and reprogramming of cell pluripotency 9, 10, 11. Recently, reports suggest that long non-coding RNA (lncRNA), non-coding RNA longer than 200 nucleotides, can also modulate gene expression through several not fully characterized mechanisms 8. EMT leads to reversible reprogramming of cells, which is defined by fundamental changes initiated and maintained by critical genes, their regulatory circuits, and signaling pathways 6.ĮMT is regulated at the transcriptional level by EMT-inducing transcription factors and at the post-transcriptional level by non-coding RNA, such as microRNA (miRNA) 7. Evidence indicates the ability of ovarian cancer cells to invade and metastasize is enhanced through the loss of epithelial features and the gain of a mesenchymal phenotype known as epithelial-to-mesenchymal transition (EMT) 4, 5. The high mortality of ovarian cancer is primarily due to the high rate of therapy resistance and the diagnosis of the disease after it has metastasized, which occurs in ~80% of women 2, 3. Ovarian cancer is the most lethal gynecologic malignancy in the United States with ~14,100 deaths and 22,500 new cases estimated for 2017 1. Therefore, our results elucidate lncRNA that regulate EMT and demonstrate DNM3OS specifically contributes to EMT in ovarian cancer. TWIST1 overexpression and DNM3OS amplification provides an explanation for increased DNM3OS levels. Proteotranscriptomic characterization further supports the DNM3OS and ovarian cancer EMT connection. DNM3OS knockdown results in altered EMT-linked genes/pathways, mesenchymal-to-epithelial transition, and reduced cell migration and invasion.
DNM3OS overexpression, but not MEG3 or MIAT, significantly correlates to worse overall patient survival. Genome-wide mapping shows 73% of MEG3-regulated EMT-linked pathway genes contain MEG3 binding sites. Here we report an integrated analysis of >700 ovarian cancer molecular profiles, including genomic data sets, from four patient cohorts identifying lncRNA DNM3OS, MEG3, and MIAT overexpression and their reproducible gene regulation in ovarian cancer EMT. Ovarian cancer is usually diagnosed after metastasis. Little is understood about the contribution of lncRNA to epithelial-to-mesenchymal transition (EMT), which correlates with metastasis. Long non-coding RNA (lncRNA) are emerging as contributors to malignancies.