Abstract
BackgroundNon-coding circular RNAs (circRNAs) have displayed dysregulated expression in several human cancers. Here, we profiled the circRNA expression of papillary thyroid carcinoma (PTC) tumors to improve our understanding of PTC pathogenesis.MethodsMicroarray profiling was performed on 18 thyroid samples, consisting of six PTC tumors, six matching contralateral normal samples, and six benign thyroid lesions. After low-intensity filtering, hierarchical clustering revealed the circRNA expression patterns. Statistical analysis followed by qRT-PCR validation identified the differential circRNAs. MicroRNA (miRNA) target prediction software identified putative miRNA response elements (MREs), which were used to construct a network map of circRNA-miRNA interactions for the differential circRNAs. Bioinformatics platforms predicted cancer-related circRNA-miRNA associations and putative downstream target genes, respectively.ResultsA total of 88 circRNAs and 10 circRNAs were significantly upregulated and downregulated, respectively, in PTC tumors relative to normal thyroid tissue, while 129 circRNAs and 226 circRNAs were significantly upregulated and downregulated, respectively, in PTC tumors relative to benign thyroid lesions. A total of 12 upregulated and four downregulated circRNAs were overlapping between the foregoing comparisons. One downregulated circRNA (hsa_circRNA_100395) showed interactive potential with two cancer-related miRNAs (miR-141-3p and miR-200a-3p). From this analysis, we identified several promising cancer-related genes that may be targets of the dysregulated hsa_circRNA_100395/miR-141-3p/miR-200a-3p axis in PTC tumors.ConclusionscircRNA dysregulation may play a role in PTC pathogenesis, and several key circRNAs show promise as candidate biomarkers for PTC. The hsa_circRNA_100395/miR-141-3p/ miR-200a-3p axis may be involved in the pathogenesis of PTC.
Highlights
Thyroid carcinoma is the most common endocrine cancer with most countries showing mortality rates of 0.2–0.4 per 100,000 men and 0.2–0.6 per 100,000 women [1]
Conclusions circRNA dysregulation may play a role in papillary thyroid carcinoma (PTC) pathogenesis, and several key circRNAs show promise as candidate biomarkers for PTC
The hsa_circRNA_100395/miR-141-3p/ miR-200a-3p axis may be involved in the pathogenesis of PTC
Summary
Thyroid carcinoma is the most common endocrine cancer with most countries showing mortality rates of 0.2–0.4 per 100,000 men and 0.2–0.6 per 100,000 women [1]. Most countries have displayed a rising incidence of thyroid cancer (mainly papillary carcinomas) over the past several decades, which has been attributed to improved diagnostic techniques over this time period [1] Despite these improved diagnostic methods, the gold standard technique—fineneedle aspiration (FNA) cytology–only yields determinate findings at a ~70% success rate [2]. In order to reduce the rate of invasive and costly diagnostic thyroidectomies, the development of alternative non-invasive diagnostic approaches as adjuncts to FNA cytology remains a pressing clinical challenge [2] To this end, the dysregulated expression of non-coding, single-stranded RNAs termed microRNAs (miRNAs, miRs) have been closely associated with the pathogenesis of human cancers, as miRNAs have been shown to regulate cellular phenomena associated with oncogenesis, including cellular differentiation, adhesion, and apoptosis [2].
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