Contribution De La Régulation post-transcriptionnelle À L’émergence De Maladies

Nguyen-Chi, Maï; Morello, Dominique

doi:10.1051/medsci/2008243290

Cited by 11 publications

(4 citation statements)

References 42 publications

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“…The mRNA of some oncogenes, such as c-fos and c-myc, are stabilized and overexpressed in many cancer cells, which mediates cancer cell proliferation (Aghib et al, 1990; Blancato et al, 2004; Meijlink et al, 1985). It has also been reported that Ras-induced oncogenic transformation involved in abnormal of gadd153 mRNA degradation (Rong et al, 2005) and the alteration of cyclin D1 mRNA stability has been implicated in cancer cell proliferation and cell transformation (Nguyen-Chi and Morello, 2008). For example, cyclin D1 mRNA with 3′ truncation was identified in human breast cells.…”

Section: Discussionmentioning

confidence: 99%

Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability

Zhang

Ouyang

et al. 2012

Toxicology and Applied Pharmacology

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Suberoylanilide hydroxamic acid (SAHA) inhibiting cancer cell growth has been associated with its down-regulation of cyclin D1 protein expression at transcription level or translation level. Here, we have demonstrated that SAHA inhibited EGF-induced Cl41 cell transformation via the decrease of cyclin D1 mRNA stability and induction of G0/G1 growth arrest. We found that SAHA treatment resulted in the dramatic inhibition of EGF-induced cell transformation, cyclin D1 protein expression and induction of G0/G1 growth arrest. Further studies showed that SAHA downregulation of cyclin D1 was only observed with endogenous cyclin D1, but not with reconstitutionally expressed cyclin D1 in the same cells, excluding the possibility of SAHA regulating cyclin D1 at level of protein degradation. Moreover, SAHA inhibited EGF-induced cyclin d1 mRNA level, whereas it did not show any inhibitory effect on cyclin D1 promoter-driven luciferase reporter activity under the same experimental conditions, suggesting that SAHA may decrease cyclin D1 mRNA stability. This notion was supported by the results that treatment of cells with SAHA decreased the half-life of cyclin D1 mRNA from 6.95 h to 2.57 h. Consistent with downregulation of cyclin D1 mRNA stability, SAHA treatment also attenuated HuR expression, which has been well-characterized as a positive regulator of cyclin D1 mRNA stability. Thus, our study identifies a novel mechanism responsible for SAHA inhibiting cell transformation via decreasing cyclin D1 mRNA stability and induction of G0/G1 growth arrest in Cl41 cells.

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Section: Discussionmentioning

confidence: 99%

Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability

Zhang

Ouyang

et al. 2012

Toxicology and Applied Pharmacology

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“…In closing, cancer is among the most prominent age-related diseases, and there is increasing recognition that TTR-RBPs can modulate oncogenesis [75, 76]. The pro-malignant influence of HuR and AUF1 is well established, and numerous cancer-related mRNA targets for these TTR-RBPs have been identified [15,28].…”

Section: Discussionmentioning

confidence: 99%

Tissue- and age-dependent expression of RNA-binding proteins that influence mRNA turnover and translation

Masuda¹,

Marasa²,

Martindale³

et al. 2009

Aging

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Gene expression patterns vary dramatically in a tissue-specific and age-dependent manner. RNA-binding proteins that regulate mRNA turnover and/or translation (TTR-RBPs) critically affect the subsets of expressed proteins. However, very little is known regarding the tissue- and age-dependent expression of TTR-RBPs in humans. Here, we use human tissue arrays containing a panel of organ biopsies from donors of different ages, to study the distribution and abundance of four TTR-RBPs: HuR, AUF1, TIA-1, and TTP. HuR and AUF1 were expressed with remarkably similar patterns. Both TTR-RBPs were present in high percentages of cells and displayed elevated intensities in many age groups and tissues, most notably in the gastrointestinal and reproductive systems; they were moderately expressed in the urinary and immune systems, and were almost undetectable in muscle and brain. TIA-1 was also abundant in many tissues and age groups; TIA-1 was expressed at high levels in the gastrointestinal, immune, urinary, and reproductive systems, and at low levels in brain and muscle. By contrast, TTP-expressing cells, as well as TTP signal intensities declined with advancing age, particularly in the immune, nervous, and muscular systems; however, TTP levels remained elevated in the gastrointestinal tract. The widespread abundance of HuR, AUF1, and TIA-1 throughout the body and in all age groups was in stark contrast with their declining levels in human diploid fibroblasts (HDFs) undergoing replicative senescence, a cultured-cell model of aging. Conversely, TTP levels increased in senescent HDFs, while TTP levels decreased with advancing age. Our studies provide a framework for the study of human TTR-RBP function in different tissues, throughout the human life span.

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“…Alterações genéticas observadas em diversos tipos de câncer são capazes de desregular o nível de expressão do mRNA mutado. (Nguyen-Chi & Morello, 2008) Uma proteína em particular, HuR, está envolvida na estabilização de mRNAs que contém ARE e participa de processos de sinalização como o da inflamação.…”

Section: 6 -Influência Da Cauda Poli(a) Na Traduçãounclassified

“…A descoberta de que a região 3'UTR contém elementos de regulação cruciais(para a expressão dos genes) oferece uma nova dimensão ao estudo dos cânceres, doenças auto-imunes e inflamatórias. Diversos campos de pesquisa foram abertos para o estudo das sequências em c/s (ARE) e dos fatores em frans, as proteínas ligantes de AU e os moRNAs (Nguyen-Chi & Morello, 2008).…”

Section: -Discussãounclassified

Estudo da poliadenilação alternativa: efeito dos polimorfismos nos elementos em cis no RNA e de transcritos em antissenso

Ezquina¹

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Alternative polyadenylation study: Effects of polymorphisms in RNA's c/s elements and antisense transcriptsCleavage and polyadenylation are essential processes involved in mRNA formation, establishing 3' end and assuring mRNA stability, its cytoplasmic location and translation. The sequence elements in 3'UTR play a crucial role in the regulation of gene expression and translation.The stability of mRNAs is altered in cancer. Genetic alterations seen in severas types of cancer can disrupt the regulation of expression leveis of mutated More than 7000 human genes have alternative polyadenylation sites and site choice depends on the tissue in which it is expressed, cell cycle or exogenous factors that may influence the regulation of gene expression.We evaluated the relative occurrence of polyadenylation signals in several types of transcripts and variants. The canonical signals AATAAA and ATTAAA are the most frequent, occurring in 46% and 15% respectively, in human reference transcripts,in all genes.Among genes with alternative polyadenylation events, signal proportion is similar, nonetheless these is no signal in 20% of shorter variants against 1 1% of longervariants.While studying alternative polyadenylation one should also take care about cleavage sites downstream regions, which have an important role in the assembly of the polyadenylation machinery. So forth we came up with a score ín order to estimate the binding strength of CstF protein to the downstream region.We have seen that among alternative polyadenylated genes, canonical signals are more affected by SNPs in shorter than in longer variants.In this work we analyzed the existence of shorter and longer transcripts in a breast cancer cell culture transcriptome of HCC1954 and we also shown it is possible to differentiate polyadenylatíon variants through microarray probes. mRNA Keywords Transcriptome Polyadenylation Gene expression 3'UTR SNPs Cancer Microarray B B Agradecimentos Gostaria de agradecer à minha avó e aos meus país por todo o apoio que me deram, durante todos esses anos. Tenho certeza que sem esse suporte. em todos os aspectos possíveis, a execução desta tese não teria sido possível. Obrigada por todo o carinho, amor, atenção, respeito, abrigo e patrocínio. Agradeço ao Dr. Sandro por me receber de imediato como aluna em seu laboratório, por acreditar na minha capacidade e independência. Gostaria de agradecer a Profa Dra Suely Made e toda a equipe de seu laboratório, na faculdade de Medicina da USP, pelos dados de microarray da Codelink, e pela colaboração na interpretação dos dados e dos resultados.Agradeço a meus colegas de laboratório, pelas diversas discussões científicas, apoio e ensinamentos. Agradeço pela paciência que todos tiveram ao início de meu doutorado, ao me ensinar inúmeras coisas sobre biologia, computação e sobre a própria pós-graduação.A Capes pelo suporte financeiro.Ao instituto Ludwig pelo acolhimento e suporte tecnológico.As secretárias Patrícia, Ana Cláudia, Renata e Elíane, pela eficiência e pela ajuda com as questões burocrát...

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Contribution De La Régulation post-transcriptionnelle À L’émergence De Maladies

Cited by 11 publications

References 42 publications

Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability

Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability

Tissue- and age-dependent expression of RNA-binding proteins that influence mRNA turnover and translation

Estudo da poliadenilação alternativa: efeito dos polimorfismos nos elementos em cis no RNA e de transcritos em antissenso

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