The lncRNA RMST is drastically downregulated in anaplastic thyroid carcinomas where exerts a tumor suppressor activity impairing epithelial-mesenchymal transition and stemness.

Autor: De Martino M; Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS) 'G. Salvatore', Consiglio Nazionale delle Ricerche (CNR), Via Pansini 5, 80131, Napoli, Italy.; Dipartimento di Medicina di Precisione, Università degli Studi della Campania 'Luigi Vanvitelli', Via De Crecchio 7, 80138, Napoli, Italy., Pellecchia S; Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS) 'G. Salvatore', Consiglio Nazionale delle Ricerche (CNR), Via Pansini 5, 80131, Napoli, Italy., Esposito F; Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS) 'G. Salvatore', Consiglio Nazionale delle Ricerche (CNR), Via Pansini 5, 80131, Napoli, Italy., Liotti F; Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS) 'G. Salvatore', Consiglio Nazionale delle Ricerche (CNR), Via Pansini 5, 80131, Napoli, Italy.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli 'Federico II', Via Pansini 5, 80131, Napoli, Italy., Credendino SC; Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS) 'G. Salvatore', Consiglio Nazionale delle Ricerche (CNR), Via Pansini 5, 80131, Napoli, Italy., Prevete N; Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS) 'G. Salvatore', Consiglio Nazionale delle Ricerche (CNR), Via Pansini 5, 80131, Napoli, Italy.; Dipartimento di Scienze Mediche Traslazionali (DiSMeT), Università degli Studi di Napoli 'Federico II', Via Pansini 5, 80131, Napoli, Italy., Decaussin-Petrucci M; Service d'Anatomie et Cytologie Pathologiques, Centre de Biologie Sud, Groupement Hospitalier Lyon Sud, Universite Lyon 1, 69495, Pierre Bénite, France., Chieffi P; Dipartimento di Medicina di Precisione, Università degli Studi della Campania 'Luigi Vanvitelli', Via De Crecchio 7, 80138, Napoli, Italy., De Vita G; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli 'Federico II', Via Pansini 5, 80131, Napoli, Italy., Melillo RM; Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS) 'G. Salvatore', Consiglio Nazionale delle Ricerche (CNR), Via Pansini 5, 80131, Napoli, Italy.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli 'Federico II', Via Pansini 5, 80131, Napoli, Italy., Fusco A; Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS) 'G. Salvatore', Consiglio Nazionale delle Ricerche (CNR), Via Pansini 5, 80131, Napoli, Italy. alfusco@unina.it.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli 'Federico II', Via Pansini 5, 80131, Napoli, Italy. alfusco@unina.it.; Instituto Nacional de Cancer, 37908, Laboratorio de Carcinogênese Molecular, Rua Andre Cavalcanti 37, Centro, 20231-050, Rio de Janeiro, Brazil. alfusco@unina.it., Pallante P; Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS) 'G. Salvatore', Consiglio Nazionale delle Ricerche (CNR), Via Pansini 5, 80131, Napoli, Italy. pallante@ieos.cnr.it.
Jazyk: angličtina
Zdroj: Cell death discovery [Cell Death Discov] 2023 Jul 01; Vol. 9 (1), pp. 216. Date of Electronic Publication: 2023 Jul 01.
DOI: 10.1038/s41420-023-01514-x
Abstrakt: Thyroid cancer is the most prevalent endocrine malignancy and comprises a wide range of lesions subdivided into differentiated (DTC) and undifferentiated thyroid cancer (UTC), mainly represented by the anaplastic thyroid carcinoma (ATC). This is one of the most lethal malignancies in humankind leading invariably to patient death in few months. Then, a better comprehension of the mechanisms underlying the development of ATC is required to set up new therapeutic approaches. Long non-coding RNAs (lncRNAs) are transcripts over 200 nucleotides in length that do not code for proteins. They show a strong regulatory function at both transcriptional and post-transcriptional level and are emerging as key players in regulating developmental processes. Their aberrant expression has been linked to several biological processes, including cancer, making them potential diagnostic and prognostic markers. We have recently analyzed the lncRNA expression profile in ATC through a microarray technique and have identified rhabdomyosarcoma 2-associated transcript (RMST) as one of the most downregulated lncRNA in ATC. RMST has been reported to be deregulated in a series of human cancers, to play an anti-oncogenic role in triple-negative breast cancer, and to modulate neurogenesis by interacting with SOX2. Therefore, these findings prompted us to investigate the role of RMST in ATC development. In this study we show that RMST levels are strongly decreased in ATC, but only slightly in DTC, indicating that the loss of this lncRNA could be related to the loss of the differentiation and high aggressiveness. We also report a concomitant increase of SOX2 levels in the same subset of ATC, that inversely correlated with RMST levels, further supporting the RMST/SOX2 relationship. Finally, functional studies demonstrate that the restoration of RMST in ATC cells reduces cell growth, migration and the stemness properties of ATC stem cells. In conclusion, these findings support a critical role of RMST downregulation in ATC development.
(© 2023. The Author(s).)
Databáze: MEDLINE
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