Genome-Wide Expression Screening Discloses Long Noncoding RNAs Involved in Thyroid Carcinogenesis.

Liyanarachchi S, Li W, Yan P, Bundschuh R, Brock P, Senter L, Ringel MD, de la Chapelle A, He H
J Clin Endocrinol Metab 101 4005-4013 11/01/2016

Abstract

CONTEXT: Long noncoding RNAs (lncRNAs) regulate pathological processes, yet their potential roles in papillary thyroid carcinoma (PTC) are poorly understood.

OBJECTIVE: To profile transcriptionally dysregulated lncRNAs in PTC and identify lncRNAs associated with clinicopathological characteristics.

DESIGN: We performed RNA sequencing of 12 paired PTC tumors and matched noncancerous tissues and correlated the expression of lncRNAs with clinical parameters. The 2 most significantly dysregulated lncRNAs were studied in an Ohio PTC cohort (n = 109) and in PTC data (n = 497) from The Cancer Genome Atlas.

SETTING: A combination of laboratory-based studies and computational analysis using clinical data and samples and a publically available database.

MAIN OUTCOME MEASURES: Correlation between expression values and clinical parameters.

RESULTS: We identified 218 lncRNAs showing differential expression in PTC (fold change ≥ 2.0, P < .01). Significant correlation was observed between the expression of 2 lncRNAs (XLOC_051122 and XLOC_006074) and 1) lymph node metastasis (N stage) and 2) BRAF(V600E) mutation. Among patients with wild-type BRAF, the expression of these 2 lncRNAs showed significantly higher levels in the patients with lymph node metastasis. In silico analysis of these lncRNAs pinpointed cell movement and cellular growth and proliferation as targeted functions.

CONCLUSIONS: Comprehensive expression screening identified 2 novel lncRNAs associated with risk factors of adverse prognosis in PTC patients. These lncRNAs may be novel players in PTC carcinogenesis.

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