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

• Published in: Nature communications Vol. 8; no. 1; pp. 1604 - 12
• Main Authors: Mitra, Ramkrishna, Chen, Xi, Greenawalt, Evan J., Maulik, Ujjwal, Jiang, Wei, Zhao, Zhongming, Eischen, Christine M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17-11-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114/2114; 692/4028/67/1517; Adult; Aged; Aged, 80 and over; Binding sites; Cancer; Cell adhesion & migration; Cell migration; Decoding; Epithelial-Mesenchymal Transition - genetics; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene mapping; Gene regulation; Genes; Humanities and Social Sciences; Humans; Kaplan-Meier Estimate; Mesenchyme; Metastases; Metastasis; MicroRNAs - genetics; Middle Aged; multidisciplinary; Non-coding RNA; Ovarian cancer; Ovarian Neoplasms - genetics; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; Science; Science (multidisciplinary); Signal Transduction - genetics; Young Adult
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-01781-0

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.
The role of lncRNA is unclear with respect to epithelial-to-mesenchymal transition (EMT), which is linked to ovarian cancer metastasis. Here, the authors show lncRNA
DNM3OS
expression contributes to ovarian cancer EMT, cell migration/invasion, and correlates with worse overall patient survival.