Profile and clinical implication of circular RNAs in human papillary thyroid carcinoma

Huihui Ren; Zhelong Liu; Siyue Liu; Xinrong Zhou; Hong Wang; Jinchao Xu; Daowen Wang; Gang Yuan

doi:10.7717/peerj.5363

Profile and clinical implication of circular RNAs in human papillary thyroid carcinoma

PeerJ. 2018 Aug 7:6:e5363. doi: 10.7717/peerj.5363. eCollection 2018.

Authors

Huihui Ren^#¹, Zhelong Liu^#¹, Siyue Liu¹, Xinrong Zhou¹, Hong Wang², Jinchao Xu², Daowen Wang^{1

2}, Gang Yuan¹

Affiliations

¹ Department of Internal Medicine, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
² Molecular Diagnostic Laboratory, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

^# Contributed equally.

Abstract

Background: Differently expressed circular RNAs (circRNAs) have been reported to play a considerable role in tumor behavior; however, the expression profile and biological function of circRNAs in papillary thyroid carcinoma (PTC) remains unknown. Thus, the study was aimed to characterize the circRNA expression profile to comprehensively understand the biological behavior of PTC.

Methods: We investigated the expression profile of circRNAs using circRNA microarray in three pairs of PTC and adjacent normal tissues. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate eight candidate circRNAs in 40 paired PTC tumors and adjacent normal samples. Next, we employed a bioinformatics tool to identify putative miRNA and circRNA-associated downstream genes, followed by constructing a network map of circRNA-miRNA-mRNA interactions and exploring the potential role of the candidate circRNAs.

Results: In total, 206 up- and 177 downregulated circRNAs were identified in PTC tissues (fold change >1.5; P < 0.05). The expression levels of eight candidate circRNAs confirmed by qRT-PCR were significantly different between the PTC and normal samples. The downstream genes of candidate circRNAs participated in various biological processes and signaling pathways. The most up and downregulated circRNAs were hsa_circRNA_007148 and hsa_circRNA_047771. The lower expression level of hsa_circRNA_047771 was associated BRAFV600 mutation, lymph node metastasis (LNM), as well as with advanced TNM stage (all P < 0.05). The higher expression level of hsa_circRNA_007148 was significantly correlated with LNM (P < 0.05). The areas under receiver operating curve were 0.876 (95% CI [0.78-0.94]) for hsa_circRNA_047771 and 0.846 (95% CI [0.75-0.96]) for hsa_circRNA_007148.

Discussion: The study suggests that dysregulated circRNAs play a critical role in PTC pathogenesis. PTC-related hsa_circRNA_047771 and hsa_circRNA_007148 may serve as potential diagnostic biomarkers and prognostic predictors for PTC patients.

Keywords: BRAFV600E; Biological marker; Microarray; Papillary thyroid carcinoma.

Grants and funding

This work was supported by the grant from the National Natural Science Foundation of China (No. 81370941, Gang Yuan), Graduates’ Innovation Fund, Huazhong University of Science and Technology (No. 5003540003, Huihui Ren) and Thyroid Research Program of Young and Middle-aged Physicians (No.2016-N-07, Zhelong Liu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.