Analysis of the Polycomb-related lncRNAs HOTAIR and ANRIL in bladder cancer. [artículo]
Por: Martínez Fernández, Mónica [Instituto de Investigación i+12]
| Dueñas, Marta [Instituto de Investigación i+12] | Segovia, Cristina [Instituto de Investigación imas12] | Rubio, Carolina [Instituto de Investigación imas12] | Fernández, María [Instituto de Investigación imas12] | Villacampa Aubá, Felipe [Urología] | Duarte Ojeda, José Manuel [Urología] | López Calderón, Fernando F [Instituto de Investigación imas12] | Gómez Rodríguez, María José [Urología] | Castellano, Daniel [Oncología Médica] | Rosa Kehrman, Federico de la [Urología] | Rodríguez Peralto, José Luis [Anatomía Patológica] | Paramio, Jesús M [Instituto de Investigación i+12].
Colaborador(es): Instituto de Investigación imas12 | Servicio de Anatomía Patológica | Servicio de Oncología Médica | Servicio de Urología.
Editor: Clinical epigenetics, 2015Descripción: 7:109.Recursos en línea: Acceso libre Resumen: Background: Long non-coding RNAs (lncRNAs) have been claimed as key molecular players in gene expression regulation, being involved in diverse epigenetic processes. They are aberrantly expressed in various tumors, but their exact role in bladder cancer is still obscure. We have recently found a major role of the Polycomb repression complex in recurrence of non-muscle-invasive bladder cancer. Here, we report the xpression of Polycomb-related lncRNAs:antisense noncoding RNA in the INK4 locus (ANRIL) and HOX antisense intergenic RNA (HOTAIR) in these tumors.
Findings: We studied a dataset of non-invasive bladder cancer samples by quantitative reverse transcription PCR (RT-qPCR) and analyzed also invasive bladder cancer samples using TCGA data. Our results showed that, while ANRIL seemed not to have a determining role, an increased HOTAIR expression appeared in recurrent and high-graded tumors associated with poor prognosis. In addition, through genome-wide transcriptome analyses, we observed that HOTAIR-EZH2-complex-regulated genes can efficiently discriminate between non-tumoral, recurrent, and non-recurrent bladder cancer samples. We also observed a significant correlation between EZH2 and HOTAIR expression levels. Using overexpression, knockdown, and pharmacological approaches in bladder cancer cell lines, we also observed that EZH2 regulates HOTAIR expression.
Conclusions: Our findings indicate that HOTAIR expression has prognostic value for bladder cancer progression, recurrence, and survival and suggest that HOTAIR plays active roles in modulating the cancer epigenome, becoming an interesting candidate as a target for cancer diagnosis and therapy. The observed HOTAIR regulation by EZH2 and the possibility of modulating EZH2 activity with specific inhibitors open new possible paths to be explored in bladder cancer therapy.
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Artículo
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PC16788 (Navegar estantería) | Disponible |
Formato Vancouver:
Martínez Fernández M, Feber A, Dueñas M, Segovia C, Rubio C, Fernandez M et al. Analysis of the Polycomb-related lncRNAs HOTAIR and ANRIL in bladder cancer. Clin Epigenetics. 2015 Oct 8;7:109.
PMID: 26457124
PMC4599691
Contiene 27 referencias
Background: Long non-coding RNAs (lncRNAs) have been claimed as key molecular players in gene expression regulation, being involved in diverse epigenetic processes. They are aberrantly expressed in various tumors, but their exact role in bladder cancer is still obscure. We have recently found a major role of the Polycomb repression complex in recurrence of non-muscle-invasive bladder cancer. Here, we report the xpression of Polycomb-related lncRNAs:antisense noncoding RNA in the INK4 locus (ANRIL) and HOX antisense intergenic RNA (HOTAIR) in these tumors.
Findings: We studied a dataset of non-invasive bladder cancer samples by quantitative reverse transcription PCR (RT-qPCR) and analyzed also invasive bladder cancer samples using TCGA data. Our results showed that, while ANRIL seemed not to have a determining role, an increased HOTAIR expression appeared in recurrent and high-graded tumors associated with poor prognosis. In addition, through genome-wide transcriptome analyses, we observed that HOTAIR-EZH2-complex-regulated genes can efficiently discriminate between non-tumoral, recurrent, and non-recurrent bladder cancer samples. We also observed a significant correlation between EZH2 and HOTAIR expression levels. Using overexpression, knockdown, and pharmacological approaches in bladder cancer cell lines, we also observed that EZH2 regulates HOTAIR expression.
Conclusions: Our findings indicate that HOTAIR expression has prognostic value for bladder cancer progression, recurrence, and survival and suggest that HOTAIR plays active roles in modulating the cancer epigenome, becoming an interesting candidate as a target for cancer diagnosis and therapy. The observed HOTAIR regulation by EZH2 and the possibility of modulating EZH2 activity with specific inhibitors open new possible paths to be explored in bladder cancer therapy.
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