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Updated: Mar 15, 2026

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
Published on: March 5, 2019
nc886, a non-coding RNA and suppressor of PKR, exerts an oncogenic function in thyroid cancer
Eun Kyung Lee1, Seung-Hyun Hong2, Sooyong Shin3,4
1Center for Thyroid Cancer, National Cancer Center, Goyang, 410-769, Korea.
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.
Insights
Non-coding RNA nc886 promotes thyroid cancer progression independently of PKR. nc886 enhances cell proliferation, migration, and invasion, acting as an oncogene in this context.
Area of Science:
- Molecular Biology
- Oncology
- RNA Biology
Background:
- nc886 is a non-coding RNA involved in cell death via Protein Kinase RNA-activated (PKR) activation.
- nc886 expression varies in malignancies, with its role as a tumor suppressor or oncogene being debated.
- The specific function of nc886 in thyroid cancer remains unclear.
Purpose of the Study:
- To elucidate the role of nc886 in thyroid cancer progression.
- To determine if nc886's function is dependent on PKR in thyroid cancer cells.
Main Methods:
- Generated PKR knockout (KO) and PKR/nc886 double KO thyroid cell lines from Nthy-ori 3-1.
- Assessed cell proliferation, migration, and invasion in generated cell lines.
- Analyzed microarray data and correlated nc886 expression with patient survival and metastasis data from The Cancer Genome Atlas (TCGA).
Main Results:
- nc886 knockout (KO) cells exhibited reduced proliferation, migration, and invasion compared to parental PKR KO cells.
- nc886's contribution to tumor phenotypes was independent of PKR.
- nc886 KO suppressed genes linked to poor survival in thyroid cancer patients.
- Elevated nc886 expression correlated with more aggressive metastatic tumors in thyroid cancer patients.
Conclusions:
- nc886 acts as a tumor promoter in thyroid cancer.
- nc886's oncogenic role is masked by PKR-mediated cell death.
- nc886 represents a potential therapeutic target in thyroid cancer.
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