nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer

• Published in: Nature communications Vol. 9; no. 1; pp. 1166 - 14
• Main Authors: Ahn, Ji-Hye, Lee, Hyun-Sung, Lee, Ju-Seog, Lee, Yeon-Su, Park, Jong-Lyul, Kim, Seon-Young, Hwang, Jung-Ah, Kunkeaw, Nawapol, Jung, Sung Yun, Kim, Tae Jin, Lee, Kwang-Soo, Jeon, Sung Ho, Lee, Inhan, Johnson, Betty H., Choi, Jung-Hye, Lee, Yong Sun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.03.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/109; 13/89; 14/34; 14/63; 38/15; 38/23; 38/39; 38/47; 38/61; 631/337/384/521; 631/67/1517/1709; 631/80/86/2368; 82/58; Cancer; Cell Adhesion; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Cystadenocarcinoma, Serous - diagnosis; Cystadenocarcinoma, Serous - genetics; Cystadenocarcinoma, Serous - mortality; Cystadenocarcinoma, Serous - pathology; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; DNA Methylation; Drug resistance; Female; Fibrosis; Gene expression; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Mesenchyme; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; multidisciplinary; Non-coding RNA; Ovarian cancer; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - genetics; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Prognosis; Ribonuclease III - genetics; Ribonuclease III - metabolism; Ribonucleic acid; RNA; RNA, Untranslated - genetics; RNA, Untranslated - metabolism; Science; Science (multidisciplinary); Signal Transduction; Signaling; Survival Analysis; Transcriptome; Transforming growth factor; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Transforming growth factor-b
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-03556-7

Transforming growth factor-β (TGF-β) signaling and microRNAs (miRNAs) are important gene regulatory components in cancer. Usually in advanced malignant stages, TGF-β signaling is elevated but global miRNA expression is suppressed. Such a gene expression signature is well illustrated in a fibrosis (or mesenchymal) subtype of ovarian cancer (OC) that is of poor prognosis. However, the interplay between the two pathways in the OC subtype has not yet been elucidated. nc886 is a recently identified non-coding RNA implicated in several malignancies. The high expression of nc886 is associated with poor prognosis in 285 OC patients. Herein, we find that in OC nc886 expression is induced by TGF-β and that nc886 binds to Dicer to inhibit miRNA maturation. By preventing the miRNA pathway, nc886 emulates TGF-β in gene expression patterns and potentiates cell adhesion, migration, invasion, and drug resistance. Here we report nc886 to be a molecular link between the TGF-β and miRNA pathways. Ovarian cancers often display elevated TGF-β signaling but repressed miRNA expression. Here the authors identify that non-coding RNA nc886 expression is induced by TGF-β, which then binds to DICER and impairs miRNA maturation.