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Long Non-coding RNA Linc-ROR Is Upregulated in Papillary Thyroid Carcinoma

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Abstract

Long non-coding RNAs (lncRNAs) may contribute to carcinogenesis and tumor progression by regulating transcription and gene expression. The role of lncRNAs in the regulation of thyroid cancer progression is being extensively examined. Here, we analyzed three lncRNAs that were overexpressed in papillary thyroid carcinomas, long intergenic non-protein coding RNA, regulator of reprogramming (Linc-ROR, ROR) PVT1 oncogene (PVT1), and HOX transcript antisense intergenic RNA (HOTAIR) to determine their roles in thyroid tumor development and progression. ROR expression has not been previously examined in thyroid carcinomas. Tissue microarrays (TMAs) of formalin-fixed paraffin-embedded tissue sections from 129 thyroid cases of benign and malignant tissues were analyzed by in situ hybridization (ISH), automated image analysis, and real-time PCR. All three lncRNAs were most highly expressed in the nuclei of PTCs. SiRNA experiments with a PTC cell line, TPC1, showed inhibition of proliferation with siRNAs for all three lncRNAs while invasion was inhibited with siRNAs for ROR and HOTAIR. SiRNA experiments with ROR also led to increased expression of miR-145, supporting the role of ROR as an endogenous miR-145 sponge. After treatment with TGF-β, there was increased expression of ROR, PVT1, and HOTAIR in the PTC1 cell line compared to control groups, indicating an induction of their expression during epithelial to mesenchymal transition (EMT). These results indicate that ROR, PVT1, and HOTAIR have important regulatory roles during the development of PTCs.

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Acknowledgments

We kindly thank Dr. John A. Copland III (Mayo Clinic, Jacksonville, FL) for the THJ-16T and THJ-21T cell lines, Dr. Rebecca E. Schweppe (University of Colorado, Denver, CO) for the BCPAP cell line, Dr. Daniel T. Ruan (Brigham and Women’s Hospital, Boston, MA) for the TPC-1 cell line, the staff of the Translational Research in Pathology (TRIP), Flow Cytometry, 3P, and Experimental Pathology laboratories (University of Wisconsin Carbone Cancer Center Cancer Center Support Grant P30 CA014520).

Funding

This study was supported by a grant from the UW Carbone Cancer Center (RVL) and a resident research grant from the UW Pathology Department to RZ.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA

    Ranran Zhang, Heather Hardin, Wei Huang, Darya Buehler & Ricardo V. Lloyd

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  1. Ranran Zhang
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  2. Heather Hardin
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  3. Wei Huang
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  4. Darya Buehler
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  5. Ricardo V. Lloyd
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Correspondence to Ricardo V. Lloyd.

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The study received ethical approval from the local Institutional Review Board.

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The authors declare that they have no conflict of interest.

Electronic supplementary material

Supplemental Figure 1

ISH localization of HOTAIR and ROR expression in the thyroid TMA. The strongest labeling was in the PTC while the NT and ATC were similar. Bar = 100 μm. (PDF 820 kb)

Supplemental Figure 2

Three FFPE samples each from the NT, PTC and ATC groups were tested for the lncRNAs PTCSC1 (A) and SOX2OT (B) by qPCR. The PTC group was significantly downregulated for both lncRNAs compared to the NT group. Whereas, both lncRNAs were also downregulated to that of the ATC group, however, this finding was not significant. Error bars expressed as SEM. ** = p<0.01, ***=p<.001 (PDF 43 kb)

Supplemental Figure 3

TPC1 cells were transfected with 10, 30 and 50 nMol of siRNAs for PVT1, ROR and HOTAIR. Represented are optimal concentrations assessed by RT-qPCR. Error bars are expressed as SEM. * = p<0.05, ** = p<0.01. (PDF 43 kb)

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Zhang, R., Hardin, H., Huang, W. et al. Long Non-coding RNA Linc-ROR Is Upregulated in Papillary Thyroid Carcinoma. Endocr Pathol 29, 1–8 (2018). https://doi.org/10.1007/s12022-017-9507-2

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  • DOI: https://doi.org/10.1007/s12022-017-9507-2

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