Nc886, a non-coding RNA and suppressor of PKR, exerts an oncogenic function in thyroid cancer

// Eun Kyung Lee 1, * , Seung-Hyun Hong 2, * , Sooyong Shin 3, 4, * , Hyun-Sung Lee 5 , Ju-Seog Lee 6 , Eun Jung Park 7, 8 , Sun Shim Choi 9 , Jae Woong Min 9 , Daeyoon Park 1 , Jung-Ah Hwang 2 , Betty H. Johnson 3 , Sung Ho Jeon 4 , In-Hoo Kim 8 , Yeon-Su Lee 2 , Yong Sun Lee 3, 8 1 Center for Thyroid Cancer, National Cancer Center, Goyang, 410-769, Korea 2 Cancer Genomics Branch, Research Institute, National Cancer Center, Goyang, 410-769, Korea 3 Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA 4 Department of Life Science and Center for Aging and Health Care, Hallym University, Chuncheon, 200-702, Korea 5 Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA 6 Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 7 Cancer Immunology Branch, National Cancer Center, Goyang, 410-769, Korea 8 Department of Cancer System Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, 410-769, Korea 9 Division of Biomedical Convergence, College of Biomedical Science, and Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, 200–701, Korea * These authors have contributed equally to this work Correspondence to: Yeon-Su Lee, email: yslee2@ncc.re.kr Yong Sun Lee, email: yslee@utmb.edu Keywords: nc886, thyroid cancer, protein kinase R, oncogene Received: June 16, 2016      Accepted: August 19, 2016      Published: September 06, 2016 ABSTRACT nc886 is a recently identified cellular non-coding RNA and its depletion leads to acute cell death via PKR (Protein Kinase RNA-activated) activation. nc886 expression is increased in some malignancies, but silenced in others. However, the precise role of nc886/PKR is controversial: is it a tumor suppressor or an oncogene? In this study, we have clarified the role of nc886 in thyroid cancer by sequentially generating PKR knockout (KO) and PKR/nc886 double KO cell lines from Nthy-ori 3-1, a partially transformed thyroid cell line. Compared to the wildtype, PKR KO alone does not exhibit any significant phenotypic changes. However, nc886 KO cells are less proliferative, migratory, and invasive than their parental PKR KO cells. Importantly, the requirement of nc886 in tumor phenotypes is totally independent of PKR. In our microarray data, nc886 KO suppresses some genes whose elevated expression is associated with poor survival confirmed by data from total of 505 thyroid cancer patients in the Caner Genome Atlas project. Also, the nc886 expression level tends to be elevated and in more aggressively metastatic tumor specimens from thyroid cancer patients. In summary, we have discovered nc886’s tumor-promoting role in thyroid cancer which has been concealed by the PKR-mediated acute cell death.