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Nat Commun. 2017 Nov 17;8(1):1604. doi: 10.1038/s41467-017-01781-0.

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

Author information

1
Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
2
Department of Computer Science and Engineering, Jadavpur University, Jadavpur, 700032, India.
3
Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China.
4
Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
5
Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA. christine.eischen@jefferson.edu.

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.

PMID:
29150601
PMCID:
PMC5693921
DOI:
10.1038/s41467-017-01781-0
[Indexed for MEDLINE]
Free PMC Article

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