PMID- 31963578
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 1
DP  - 2020 Jan 17
TI  - 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.
LID - 10.3390/cancers12010235 [doi]
LID - 235
AB  - 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.
FAU - Pellecchia, Simona
AU  - Pellecchia S
AUID- ORCID: 0000-0001-6826-8407
AD  - Institute for Experimental Endocrinology and Oncology (IEOS) "G. Salvatore", 
      National Research Council (CNR), via S. Pansini, 5-80131 Naples, Italy.
AD  - Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of 
      Naples "Federico II" via S. Pansini, 5-80131 Naples, Italy.
FAU - Sepe, Romina
AU  - Sepe R
AUID- ORCID: 0000-0001-7162-7706
AD  - Institute for Experimental Endocrinology and Oncology (IEOS) "G. Salvatore", 
      National Research Council (CNR), via S. Pansini, 5-80131 Naples, Italy.
AD  - Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of 
      Naples "Federico II" via S. Pansini, 5-80131 Naples, Italy.
FAU - Decaussin-Petrucci, Myriam
AU  - Decaussin-Petrucci M
AD  - Service d'Anatomie et Cytologie Pathologiques, Centre de Biologie Sud, Groupement 
      Hospitalier Lyon Sud, Universite Lyon 1, 69495 Pierre Benite, France.
FAU - Ivan, Cristina
AU  - Ivan C
AD  - Department of Experimental Therapeutics, The University of Texas MD Anderson 
      Cancer Center, Houston, TX 77030, USA.
AD  - Center for RNA Interference and Non-Coding RNAs, The University of Texas MD 
      Anderson Cancer Center, Houston, TX 77030, USA.
FAU - Shimizu, Masayoshi
AU  - Shimizu M
AD  - Department of Experimental Therapeutics, The University of Texas MD Anderson 
      Cancer Center, Houston, TX 77030, USA.
AD  - Center for RNA Interference and Non-Coding RNAs, The University of Texas MD 
      Anderson Cancer Center, Houston, TX 77030, USA.
FAU - Coppola, Carmela
AU  - Coppola C
AUID- ORCID: 0000-0003-2943-8164
AD  - Scientific Directorate, Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale", 
      via M. Semmola, 80131 Naples, Italy.
FAU - Testa, Domenico
AU  - Testa D
AUID- ORCID: 0000-0001-7176-3652
AD  - 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.
FAU - Calin, George Adrian
AU  - Calin GA
AD  - Department of Experimental Therapeutics, The University of Texas MD Anderson 
      Cancer Center, Houston, TX 77030, USA.
AD  - Center for RNA Interference and Non-Coding RNAs, The University of Texas MD 
      Anderson Cancer Center, Houston, TX 77030, USA.
FAU - Fusco, Alfredo
AU  - Fusco A
AD  - Institute for Experimental Endocrinology and Oncology (IEOS) "G. Salvatore", 
      National Research Council (CNR), via S. Pansini, 5-80131 Naples, Italy.
AD  - Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of 
      Naples "Federico II" via S. Pansini, 5-80131 Naples, Italy.
FAU - Pallante, Pierlorenzo
AU  - Pallante P
AUID- ORCID: 0000-0001-7319-684X
AD  - Institute for Experimental Endocrinology and Oncology (IEOS) "G. Salvatore", 
      National Research Council (CNR), via S. Pansini, 5-80131 Naples, Italy.
LA  - eng
GR  - Epigenomics-EPIGEN/CNR Flagship Project/
PT  - Journal Article
DEP - 20200117
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7017000
OTO - NOTNLM
OT  - EZH2
OT  - PAR5
OT  - anaplastic thyroid carcinoma
OT  - long non-coding RNA
COIS- The authors declare no conflict of interests.
EDAT- 2020/01/23 06:00
MHDA- 2020/01/23 06:01
PMCR- 2020/01/17
CRDT- 2020/01/23 06:00
PHST- 2019/12/10 00:00 [received]
PHST- 2020/01/09 00:00 [revised]
PHST- 2020/01/14 00:00 [accepted]
PHST- 2020/01/23 06:00 [entrez]
PHST- 2020/01/23 06:00 [pubmed]
PHST- 2020/01/23 06:01 [medline]
PHST- 2020/01/17 00:00 [pmc-release]
AID - cancers12010235 [pii]
AID - cancers-12-00235 [pii]
AID - 10.3390/cancers12010235 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 Jan 17;12(1):235. doi: 10.3390/cancers12010235.