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

被引：166

作者：

Mitra, Ramkrishna ^{[1
]}

Chen, Xi ^{[1
]}

Greenawalt, Evan J. ^{[1
]}

Maulik, Ujjwal ^{[2
]}

Jiang, Wei ^{[3
]}

Zhao, Zhongming ^{[4
]}

Eischen, Christine M. ^{[1
]}

机构：

[1] Thomas Jefferson Univ, Dept Canc Biol, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA

[2] Jadavpur Univ, Dept Comp Sci & Engn, Jadavpur 700032, India

[3] Nanjing Univ Aeronaut & Astronaut, Dept Biomed Engn, Nanjing 211106, Jiangsu, Peoples R China

[4] Univ Texas Houston, Hlth Sci Ctr Houston, Ctr Precis Hlth, Sch Biomed Informat, Houston, TX 77030 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

TGF-BETA; EXPRESSION; GENOME; GENES; EMT; METASTASIS; INVASION; SURVIVAL; PACKAGE; GROWTH;

D O I：

10.1038/s41467-017-01781-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. Proteotran-scriptomic 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.

引用

页数：12

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