Spotlight on hTERT Complex Regulation in Cutaneous T-Cell Lymphomas

• Tipo: Artigo em Revista Científica Internacional
• Data: 2023

Autores

Ropio, J (Autor) Outra; Prochazkova Carlotti, M (Autor) Outra; Batista, R (Autor) Outra; Pestana, A (Autor) Outra; Chebly, A (Autor) Outra; Ferrer, J (Autor) Outra; Idrissi, Y (Autor) Outra; Cappellen, D (Autor) Outra; Duraes, C (Autor) Outra; Boaventura, P (Autor) Outra; Vinagre, J (Autor) Outra; Azzi Martin, L (Autor) Outra; Poglio, S (Autor) Outra; Cabecadas, J (Autor) Outra; Campos, MA (Autor) Outra; Beylot Barry, M (Autor) Outra; Sobrinho Simoes, M (Autor) Outra; Merlio, JP (Autor) Outra; Soares, P (Autor) FMUP; Chevret, E (Autor) Outra

Revista

Título: Genes

Vol. 238

Página Final: 439

ISSN: 2073-4425

Editora: MDPI

Indexação

ISI Web of Knowledge - 2 Citações

Scopus - 2 Citações

Outras Informações

ID Authenticus: P-00X-ZV9

DOI: 10.3390/genes14020439

Abstract (EN): As a major cancer hallmark, there is a sustained interest in understanding the telomerase contribution to carcinogenesis in order to therapeutically target this enzyme. This is particularly relevant in primary cutaneous T-cell lymphomas (CTCL), a malignancy showing telomerase dysregulation with few investigative data available. In CTCL, we examined the mechanisms involved in telomerase transcriptional activation and activity regulation. We analyzed 94 CTCL patients from a Franco-Portuguese cohort, as well as 8 cell lines, in comparison to 101 healthy controls. Our results showed that not only polymorphisms (SNPs) located at the promoter of human telomerase reverse transcriptase (hTERT) gene (rs2735940 and rs2853672) but also an SNP located within the coding region (rs2853676) could influence CTCL occurrence. Furthermore, our results sustained that the post-transcriptional regulation of hTERT contributes to CTCL lymphomagenesis. Indeed, CTCL cells present a different pattern of hTERT spliced transcripts distribution from the controls, mostly marked by an increase in the hTERT beta+ variants proportion. This increase seems to be associated with CTCL development and progression. Through hTERT splicing transcriptome modulation with shRNAs, we observed that the decrease in the alpha-beta+ transcript induced a decrease in the cell proliferation and tumorigenic capacities of T-MF cells in vitro. Taken together, our data highlight the major role of post-transcriptional mechanisms regulating telomerase non canonical functions in CTCL and suggest a new potential role for the alpha-beta+ hTERT transcript variant.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 16