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.
Highlights
Thyroid cancer is the most common endocrine malignancy, whose worldwide prevalence has been soaring because of advances in medical imaging technologies and easy accessibility to ultrasonography [1, 2]
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
We measured the expression of nc886 in paired normal/tumor samples from 37 thyroid cancer patients and classified into three groups according to nc886 levels (Figure 1A)
Summary
Thyroid cancer is the most common endocrine malignancy, whose worldwide prevalence has been soaring because of advances in medical imaging technologies and easy accessibility to ultrasonography [1, 2] Since it remains asymptomatic even in advanced stages, many researchers have been seeking a biomarker to distinguish more aggressive tumors from indolent ones at the time of diagnosis. Growing evidence indicates a significance for noncoding RNAs (ncRNAs) in the diagnosis and prognosis of thyroid cancer (reviewed in [3]) These ncRNAs are either small [< 50 nucleotides (nts)] or long (>200 nts) in length and play a regulatory role in gene expression by degrading target mRNAs or determining the chromatin status of target genes [4]. Nc886 is transcribed by RNA polymerase III (Pol III) whereas a majority of regulatory ncRNAs are RNA polymerase II (Pol II) products
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