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BNC2 is a putative tumor suppressor gene in high-grade serous ovarian carcinoma and impacts cell survival after oxidative stress.
Cesaratto, Laura; Grisard, Eleonora; Coan, Michela; Zandonà, Luigi; De Mattia, Elena; Poletto, Elena; Cecchin, Erika; Puglisi, Fabio; Canzonieri, Vincenzo; Mucignat, Maria Teresa; Zucchetto, Antonella; Stocco, Gabriele; Colombatti, Alfonso; Nicoloso, Milena S; Spizzo, Riccardo.
Afiliación
  • Cesaratto L; Division of Experimental Oncology2, Department of Translational Research, Centro di Riferimento Oncologico (CRO Aviano), National Cancer Institute, Aviano, Italy.
  • Grisard E; Division of Experimental Oncology2, Department of Translational Research, Centro di Riferimento Oncologico (CRO Aviano), National Cancer Institute, Aviano, Italy.
  • Coan M; Division of Experimental Oncology2, Department of Translational Research, Centro di Riferimento Oncologico (CRO Aviano), National Cancer Institute, Aviano, Italy.
  • Zandonà L; Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
  • De Mattia E; Division of Experimental Oncology2, Department of Translational Research, Centro di Riferimento Oncologico (CRO Aviano), National Cancer Institute, Aviano, Italy.
  • Poletto E; Division of Experimental and Clinical Pharmacology, Department of Translational Research Centro di Riferimento Oncologico (CRO Aviano), National Cancer Institute, Aviano, Italy.
  • Cecchin E; Department of Oncology, University Hospital of Udine, Udine, Italy.
  • Puglisi F; Division of Experimental and Clinical Pharmacology, Department of Translational Research Centro di Riferimento Oncologico (CRO Aviano), National Cancer Institute, Aviano, Italy.
  • Canzonieri V; Department of Oncology, University Hospital of Udine, Udine, Italy.
  • Mucignat MT; Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
  • Zucchetto A; Division of Pathology, Department of Translational Research, CRO Aviano National Cancer Institute, Aviano, Italy.
  • Stocco G; Division of Experimental Oncology2, Department of Translational Research, Centro di Riferimento Oncologico (CRO Aviano), National Cancer Institute, Aviano, Italy.
  • Colombatti A; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico (CRO Aviano), National Cancer Institute, Aviano, Italy.
  • Nicoloso MS; Department of Life Sciences, University of Trieste, Trieste, Italy.
  • Spizzo R; Division of Experimental Oncology2, Department of Translational Research, Centro di Riferimento Oncologico (CRO Aviano), National Cancer Institute, Aviano, Italy.
Cell Death Dis ; 7(9): e2374, 2016 09 22.
Article en En | MEDLINE | ID: mdl-27899818
Rs3814113 is the single-nucleotide polymorphism (SNP) showing the strongest association with high-grade serous ovarian carcinoma (HGSOC) incidence and is located in an intergenic region about 44 kb downstream of basonuclin 2 (BNC2) gene. Lifetime number of ovulations is associated with increased risk to develop HGSOC, probably because of cell damage of extrauterine Müllerian epithelium by ovulation-induced oxidative stress. However, the impact of low-penetrance HGSOC risk alleles (e.g. rs3814113) on the damage induced by oxidative stress remains unclear. Therefore, the purpose of this study was to investigate whether rs3814113 genetic interval regulates BNC2 expression and whether BNC2 expression levels impact on cell survival after oxidative stress. To do this, we analyzed gene expression levels of BNC2 first in HGSOC data sets and then in an isogenic cell line that we engineered to carry a 5 kb deletion around rs3814113. Finally, we silenced BNC2 and measured surviving cells after hydrogen peroxide (H2O2) treatment to simulate oxidative stress after ovulation. In this paper, we describe that BNC2 expression levels are reduced in HGSOC samples compared with control samples, and that BNC2 expression levels decrease following oxidative stress and ovulation in vitro and in vivo, respectively. Moreover, deletion of 5 kb surrounding rs3814113 decreases BNC2 expression levels in an isogenic cell line, and silencing of BNC2 expression levels increases cell survival after H2O2 treatment. Altogether, our findings suggest that the intergenic region located around rs3814113 regulates BNC2 expression, which in turn affects cell survival after oxidative stress response. Indeed, HGSOC samples present lower BNC2 expression levels that probably, in the initial phases of oncogenic transformation, conferred resistance to oxidative stress and ultimately reduced the clearance of cells with oxidative-induced damages.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Genes Supresores de Tumor / Cistadenocarcinoma Seroso / Estrés Oxidativo / Proteínas de Unión al ADN Límite: Animals / Female / Humans Idioma: En Revista: Cell Death Dis Año: 2016 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Genes Supresores de Tumor / Cistadenocarcinoma Seroso / Estrés Oxidativo / Proteínas de Unión al ADN Límite: Animals / Female / Humans Idioma: En Revista: Cell Death Dis Año: 2016 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido