nc886, a non-coding RNA and suppressor of PKR, exerts an oncogenic function in thyroid cancer.
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.
Center for Thyroid Cancer, National Cancer Center, Goyang, 410-769, Korea.
Eun Kyung
EK
Lee
Cancer Genomics Branch, Research Institute, National Cancer Center, Goyang, 410-769, Korea.
Seung-Hyun
SH
Hong
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.|Department of Life Science and Center for Aging and Health Care, Hallym University, Chuncheon, 200-702, Korea.
Sooyong
S
Shin
Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Hyun-Sung
HS
Lee
Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ju-Seog
JS
Lee
Cancer Immunology Branch, National Cancer Center, Goyang, 410-769, Korea.|Department of Cancer System Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, 410-769, Korea.
Eun Jung
EJ
Park
Division of Biomedical Convergence, College of Biomedical Science, and Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, 200-701, Korea.
Sun Shim
SS
Choi
Division of Biomedical Convergence, College of Biomedical Science, and Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, 200-701, Korea.
Jae Woong
JW
Min
Center for Thyroid Cancer, National Cancer Center, Goyang, 410-769, Korea.
Daeyoon
D
Park
Cancer Genomics Branch, Research Institute, National Cancer Center, Goyang, 410-769, Korea.
Jung-Ah
JA
Hwang
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Betty H
BH
Johnson
Department of Life Science and Center for Aging and Health Care, Hallym University, Chuncheon, 200-702, Korea.
Sung Ho
SH
Jeon
Department of Cancer System Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, 410-769, Korea.
In-Hoo
IH
Kim
Cancer Genomics Branch, Research Institute, National Cancer Center, Goyang, 410-769, Korea.
Yeon-Su
YS
Lee
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.|Department of Cancer System Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, 410-769, Korea.
Yong Sun
YS
Lee
D000328:Adult; D016923:Cell Death / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D063990:Gene Ontology; D020868:Gene Silencing; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009857:Oncogenes; D022661:RNA, Untranslated / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome; D019892:eIF-2 Kinase / Q000235:genetics*
D022661:RNA, Untranslated; C000602769:EIF2AK2 protein, human; D019892:eIF-2 Kinase
nc886; oncogene; protein kinase R; thyroid cancer