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

Eun Kyung Lee, Seung Hyun Hong, Sooyong Shin, Hyun Sung Lee, Ju Seog Lee, Eun Jung Park, Sun Shim Choi, Jae Woong Min, Daeyoon Park, Jung Ah Hwang, Betty H. Johnson, Sung Ho Jeon, In Hoo Kim, Yeon Su Lee, Yong Sun Lee

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)75000-75012
Number of pages13
JournalOncotarget
Volume7
Issue number46
DOIs
StatePublished - 2016

Keywords

  • Oncogene
  • Protein kinase R
  • Thyroid cancer
  • nc886

ASJC Scopus subject areas

  • Oncology

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    Lee, E. K., Hong, S. H., Shin, S., Lee, H. S., Lee, J. S., Park, E. J., Choi, S. S., Min, J. W., Park, D., Hwang, J. A., Johnson, B. H., Jeon, S. H., Kim, I. H., Lee, Y. S., & Lee, Y. S. (2016). Nc886, a non-coding RNA and suppressor of PKR, exerts an oncogenic function in thyroid cancer. Oncotarget, 7(46), 75000-75012. https://doi.org/10.18632/oncotarget.11852