Portal de investigación
Epigenetic Mechanisms Are Involved in the Oncogenic Properties of ZNF518B in Colorectal Cancer.
Fecha de publicación:
Fecha Ahead of Print:
Autores de INCLIVA
Participantes ajenos a INCLIVA
- Riffo-Campos, AL
- Franco, L
Grupos y Plataformas de I+D+i
Abstract
The ZNF518B gene, which is up-regulated in colorectal cancer, plays a role in cell dissemination and metastasis. It encodes a zinc-finger protein, which interacts with histone methyltransferases G9A and EZH2. The expression of the two major mRNA isoforms 1 (coding for the full protein) and 2 was quantified by RT-qPCR in a cohort of 66 patients. The effects of silencing ZNF518B on the transcriptome of DLD1 and HCT116 cells were analysed by Clariom-S assays and validated by RT-qPCR. The recruitment of methyltransferases and the presence of H3K27me3 were studied by chromatin immunoprecipitation (ChIP). The ratio (isoform 2)/(isoform 1) negatively correlated with the relapsing of disease. The study of the transcriptome of DLD1 and HCT116 cells revealed that many genes affected by silencing ZNF518B are related to cancer. After crossing these results with the list of genes affected by silencing the histone methyltransferases (retrieved in silico), five genes were selected. ChIP analysis revealed that the recruitment of EZH2 is ZNF518B-dependent in KAT2B, RGS4 and EFNA5; the level of H3K27me3 changes in accordance. G9A also binds RGS4 and PADI3 in a ZNF518B-dependent manner. The results highlight the importance of epigenetics in cancer and open a novel therapeutic possibility, as inhibition of histone methyltransferases may reverse the disease-linked histone marks.
Datos de la publicación
- ISSN/ISSNe:
- 2072-6694, 2072-6694
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 33801071
Cancers MDPI
Citas Recibidas en Web of Science: 8
Documentos
Filiaciones
Keywords
- EZH2; G9A; alternative splicing; cell dissemination and metastasis; colorectal cancer; histone methylation; relapse
Proyectos y Estudios Clínicos
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Investigador Principal: ANDRÉS CERVANTES RUIPEREZ
PI15/02180 . INSTITUTO SALUD CARLOS III . 2016
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Cita
Gimeno F,Riffo AL,Torres L,Tarazona N,Gambardella V,Cervantes A,Lopez G,Franco L,Castillo J. Epigenetic Mechanisms Are Involved in the Oncogenic Properties of ZNF518B in Colorectal Cancer. Cancers. 2021. 13. (6):1433. IF:6,575. (1).
Epigenetic Mechanisms Are Involved in the Oncogenic Properties of ZNF518B in Colorectal Cancer. Gimeno F, Riffo AL, Torres L, Tarazona N, Gambardella V, Cervantes A, Lopez G et al. Cancers. 2021 marzo 21. 13 (6):DOI:10.3390/cancers13061433. PMID:33801071.
