Decoding critical long non-coding RNA in ovarian cancer epithelial-to-mesenchymal transition

Ramkrishna Mitra, Xi Chen, Evan J. Greenawalt, Ujjwal Maulik, Wei Jiang, Zhongming Zhao and Christine M. Eischen ()
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Ramkrishna Mitra: Sidney Kimmel Cancer Center, Thomas Jefferson University
Xi Chen: Sidney Kimmel Cancer Center, Thomas Jefferson University
Evan J. Greenawalt: Sidney Kimmel Cancer Center, Thomas Jefferson University
Ujjwal Maulik: Jadavpur University
Wei Jiang: Nanjing University of Aeronautics and Astronautics
Zhongming Zhao: The University of Texas Health Science Center at Houston
Christine M. Eischen: Sidney Kimmel Cancer Center, Thomas Jefferson University

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract Long non-coding RNA (lncRNA) are emerging as contributors to malignancies. Little is understood about the contribution of lncRNA to epithelial-to-mesenchymal transition (EMT), which correlates with metastasis. Ovarian cancer is usually diagnosed after metastasis. 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. Genome-wide mapping shows 73% of MEG3-regulated EMT-linked pathway genes contain MEG3 binding sites. DNM3OS overexpression, but not MEG3 or MIAT, significantly correlates to worse overall patient survival. DNM3OS knockdown results in altered EMT-linked genes/pathways, mesenchymal-to-epithelial transition, and reduced cell migration and invasion. Proteotranscriptomic characterization further supports the DNM3OS and ovarian cancer EMT connection. TWIST1 overexpression and DNM3OS amplification provides an explanation for increased DNM3OS levels. Therefore, our results elucidate lncRNA that regulate EMT and demonstrate DNM3OS specifically contributes to EMT in ovarian cancer.

Date: 2017
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DOI: 10.1038/s41467-017-01781-0

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