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Open AccessArticle

The Long Non-Coding RNA Prader Willi/Angelman Region RNA5 (PAR5) Is Downregulated in Anaplastic Thyroid Carcinomas Where It Acts as a Tumor Suppressor by Reducing EZH2 Activity

1
Institute for Experimental Endocrinology and Oncology (IEOS) “G. Salvatore”, National Research Council (CNR), via S. Pansini, 5-80131 Naples, Italy
2
Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples “Federico II” via S. Pansini, 5-80131 Naples, Italy
3
Service d’Anatomie et Cytologie Pathologiques, Centre de Biologie Sud, Groupement Hospitalier Lyon Sud, Universite Lyon 1, 69495 Pierre Bénite, France
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Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
5
Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Scientific Directorate, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
7
Otorhinolaryngology, Head and Neck Surgery Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, via S. Pansini, 5-80131 Naples, Italy
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(1), 235; https://doi.org/10.3390/cancers12010235
Received: 10 December 2019 / Revised: 9 January 2020 / Accepted: 14 January 2020 / Published: 17 January 2020
(This article belongs to the Special Issue Thyroid Cancer)
Anaplastic thyroid carcinoma (ATC) represents one the most aggressive neoplasias in humans, and, nowadays, limited advances have been made to extend the survival and reduce the mortality of ATC. Thus, the identification of molecular mechanism underlying its progression is needed. Here, we evaluated the long non-coding RNA (lncRNA) expression profile of nine ATC in comparison with five normal thyroid tissues by a lncRNA microarray. By this analysis, we identified 19 upregulated and 28 downregulated lncRNAs with a fold change >1.1 or <−1.1 and p-value < 0.05, in ATC samples. Some of them were subsequently validated by qRT-PCR. Then, we investigated the role of the lncRNA Prader Willi/Angelman region RNA5 (PAR5), drastically and specifically downregulated in ATC. The restoration of PAR5 reduces proliferation and migration rates of ATC-derived cell lines indicating that its downregulation contributes to thyroid cancer progression. Our results suggest that PAR5 exerts its anti-oncogenic role by impairing Enhancer of Zeste Homolog 2 (EZH2) oncogenic activity since we demonstrated that PAR5 interacts with it in thyroid cancer cell lines, reducing EZH2 protein levels and its binding on the E-cadherin promoter, relieving E-cadherin from the negative regulation by EZH2. Consistently, EZH2 is overexpressed in ATC, but not in differentiated thyroid carcinomas. The results reported here define a tumor suppressor role for PAR5 in undifferentiated thyroid neoplasias, further highlighting the pivotal role of lncRNAs in thyroid carcinogenesis. View Full-Text
Keywords: anaplastic thyroid carcinoma; EZH2; PAR5; long non-coding RNA anaplastic thyroid carcinoma; EZH2; PAR5; long non-coding RNA
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Pellecchia, S.; Sepe, R.; Decaussin-Petrucci, M.; Ivan, C.; Shimizu, M.; Coppola, C.; Testa, D.; Calin, G.A.; Fusco, A.; Pallante, P. The Long Non-Coding RNA Prader Willi/Angelman Region RNA5 (PAR5) Is Downregulated in Anaplastic Thyroid Carcinomas Where It Acts as a Tumor Suppressor by Reducing EZH2 Activity. Cancers 2020, 12, 235.

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