Microarray profiling of circular RNAs in human papillary thyroid carcinoma

PLoS One. 2017 Mar 13;12(3):e0170287. doi: 10.1371/journal.pone.0170287. eCollection 2017.

Abstract

Background: Non-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.

Methods: Microarray 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.

Results: A 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.

Conclusions: circRNA 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.

Publication types

  • Validation Study

MeSH terms

  • Carcinoma / genetics*
  • Carcinoma, Papillary
  • Humans
  • Oligonucleotide Array Sequence Analysis*
  • RNA / genetics*
  • RNA, Circular
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / genetics*

Substances

  • RNA, Circular
  • RNA

Grants and funding

This work was supported by the Chinese Medical Association, clinical research and special project funds (grant no. 12020130273) and the Provincial Governor's Special Fund of Guizhou Province (grant no. 2012100). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Microarray experiments were performed by KangChen Bio-tech, Shanghai, China.