Publicação
The role of macroH2A1 in prostate carcinogenesis
| Resumo: | Prostate cancer (PCa) is the most common noncutaneous malignancy in men and the major cause of cancer-related morbidity and mortality worldwide. Due to genetic and epigenetic deregulations, prostate cancer is characteristically asymptomatic in early stages. Deeper understanding of this mechanisms strength the development of new and improved diagnostic and prognostic tools and, therefore, better treatment strategies. The shuffle of canonical histones, an epigenetic mechanism, is highly conserved among species and expression alterations of these histones variants, such as macroH2A1, are related to cancer development. H2AFY gene codifies two isoforms of the H2A histone variant macroH2A1: macroH2A1.1 and macroH2A1.2. MacroH2A1.1 inhibits cell proliferation and cell migration, whilst macroH2A1.2 has opposite functions. To date, there were studies of this histone variant in several cancer types, but none in PCa. Thus, our aim was to assess whether macroH2A1 is implicated in prostate carcinogenesis. In a large series of prostate samples from Portuguese Oncology Institute-Porto, we found that macroH2A1.1 transcript levels were downregulated in high-grade prostatic intraepithelial neoplasia (PIN) and primary PCa compared to normal prostatic tissues. Moreover, QKI, a splicing regulator that induces macroH2A1.1 expression, presented similar results. Compared with clinicopathological data, macroH2A1.1 and QKI expression were associated with Gleason Score and PSA blood levels. Both transcripts were able to discriminate cancerous from noncancerous prostate tissues. MacroH2A1.1 in vitro overexpression in a PCa Cell line decreased cell viability. Thus, macroH2A1.1 seems to play a critical role in PCa development. |
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| Autores principais: | Silva, Tânia Soraia Vieira da |
| Assunto: | Cancer Epigenetic Isoforms MacroH2A1 Prostate QKI Splicing regulators Cancro Epigenética Isoformas Próstata Reguladores de slincing |
| Ano: | 2015 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Prostate cancer (PCa) is the most common noncutaneous malignancy in men and the major cause of cancer-related morbidity and mortality worldwide. Due to genetic and epigenetic deregulations, prostate cancer is characteristically asymptomatic in early stages. Deeper understanding of this mechanisms strength the development of new and improved diagnostic and prognostic tools and, therefore, better treatment strategies. The shuffle of canonical histones, an epigenetic mechanism, is highly conserved among species and expression alterations of these histones variants, such as macroH2A1, are related to cancer development. H2AFY gene codifies two isoforms of the H2A histone variant macroH2A1: macroH2A1.1 and macroH2A1.2. MacroH2A1.1 inhibits cell proliferation and cell migration, whilst macroH2A1.2 has opposite functions. To date, there were studies of this histone variant in several cancer types, but none in PCa. Thus, our aim was to assess whether macroH2A1 is implicated in prostate carcinogenesis. In a large series of prostate samples from Portuguese Oncology Institute-Porto, we found that macroH2A1.1 transcript levels were downregulated in high-grade prostatic intraepithelial neoplasia (PIN) and primary PCa compared to normal prostatic tissues. Moreover, QKI, a splicing regulator that induces macroH2A1.1 expression, presented similar results. Compared with clinicopathological data, macroH2A1.1 and QKI expression were associated with Gleason Score and PSA blood levels. Both transcripts were able to discriminate cancerous from noncancerous prostate tissues. MacroH2A1.1 in vitro overexpression in a PCa Cell line decreased cell viability. Thus, macroH2A1.1 seems to play a critical role in PCa development. |
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