nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer
 Authors and Affiliations
 Authors and Affiliations
Ji-Hye Ahn1, Hyun-Sung Lee2, Ju-Seog Lee3, Yeon-Su Lee4, Jong-Lyul Park5, Seon-Young Kim5, Jung-Ah Hwang6, Nawapol Kunkeaw7,8, Sung Yun Jung9, Tae Jin Kim10, Kwang-Soo Lee11, Sung Ho Jeon11, Inhan Lee12, Betty H. Johnson7, Jung-Hye Choi1,* & Yong Sun Lee7,13,*
1Department of Life and Nanopharmaceutical Sciences and Department of Oriental Pharmaceutical Science, Kyung Hee University, Seoul 02447, Korea. 2Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA. 3Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 4 Rare Cancer Branch, Research Institute, National Cancer Center, Goyang 10408, Korea. 5 Medical Genomics Research Center, KRIBB, Daejeon 34141, Korea. 6Genomics Core Laboratory, Omics Core Laboratory, Research Institute, National Cancer Center, Goyang 10408, Korea. 7Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston TX77555-1072, USA. 8 Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand. 9 Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA. 10Department of Obstetrics and Gynecology, Cheil General Hospital and Women’s Healthcare Center, College of Medicine Dankook University, Seoul 04619, Korea. 11Department of Life Science and Center for Aging and Health Care, Hallym University, Chuncheon 24252, Korea. 12miRcore, Ann Arbor, MI 48105, USA. 13Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Korea.
*Correspondence to Jung-Hye Choi or Yong Sun Lee
Abstract 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.
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