Data/hora: 09/06/2024 18:30:06

Provedor de dados: | 56
País: | Brazil
Título: | Modulation of the prostaglandin-endoperoxide synthase 2 gene expression by variant haplotypes: influence of the 3′-untranslated region
Autores: | Piranda,D.N.; Abreu,R.B.V.; Freitas-Alves,D.R.; de Carvalho,M.A.; Vianna-Jorge,R.
Data: | 2018-01-01
Ano: | 2018
Palavras-chave: | COX-2; PTGS2; Haplotypes; Gene expression; MCF-7; HEK293FT.
Resumo: | The inducible inflammatory enzyme cycloxigenase-2 is up-regulated in cancer, and favors tumor progression. Cycloxigenase-2 is encoded by the prostaglandin-endoperoxide synthase 2 (PTGS2) gene, which presents sequence variations in the promoter region (PR) and in the 3′-untranslated region (3′-UTR). Different PR (rs689465, rs689466, rs20417) and 3′-UTR (rs5275) variants were generated by site-directed mutagenesis, and combined in haplotypes to access expression levels using a reporter system (luciferase) in human cells (MCF-7 and HEK293FT). Luciferase activity did not differ significantly among PTGS2 PR constructs, except for pAAC (containing variant allele rs20417 C), with 40% less activity than pAAG (wild-type sequence) in MCF-7 cells (P&lt;0.01). Despite the lack of individual significant differences, PTGS2 PR constructs enclosing rs689466 G (pAGG and pAGC) showed an approximate two-fold increase in luciferase activity when compared to those containing rs689466 A (pAAG, pGAC, pAAC and pGAG) in both cell lines (P&lt;0.001 for MCF-7 and P=0.03 for HEK293FT). The effect of PTGS2 3′-UTR sequences varied between MCF-7 and HEK293FT: MCF-7 cells showed significant reduction (40–60%) in luciferase activity (at least P&lt;0.01), whereas HEK293FT cells showed more diverse results, with an average 2-fold increase when combined constructs (PR and 3′-UTR) were compared to respective parental PR sequences. The contribution of 3′-UTR variant (rs5275) was not consistent in either cell line. Despite the modulation of the 3′-UTR, with variable effects of rs5275, the enhancing transcriptional effect of rs689466 G was still detectable (P&lt;0.0001 in MCF-7 or P=0.03 in HEK293FT cells).
Tipo: | Info:eu-repo/semantics/article
Idioma: | Inglês
Identificador: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2018000200602
Editor: | Associação Brasileira de Divulgação Científica
Relação: | 10.1590/1414-431x20176546
Formato: | text/html
Fonte: | Brazilian Journal of Medical and Biological Research  v.51 n.2 2018
Fonte: | info:eu-repo/semantics/openAccess