Dynamic chromosomal tuning of a novel GAU1 lncing driver at chr12p13.32 accelerates tumorigenesis.
Nucleic Acids Res
; 46(12): 6041-6056, 2018 07 06.
Article
em En
| MEDLINE
| ID: mdl-29741668
ABSTRACT
Aberrant chromatin transformation dysregulates gene expression and may be an important driver of tumorigenesis. However, the functional role of chromosomal dynamics in tumorigenesis remains to be elucidated. Here, using in vitro and in vivo experiments, we reveal a novel long noncoding (lncing) driver at chr12p13.3, in which a novel lncRNA GALNT8 Antisense Upstream 1 (GAU1) is initially activated by an open chromatin status, triggering recruitment of the transcription elongation factor TCEA1 at the oncogene GALNT8 promoter and cis-activates the expression of GALNT8. Analysis of The Cancer Genome Atlas (TCGA) clinical database revealed that the GAU1/GALNT8 driver serves as an important indicative biomarker, and targeted silencing of GAU1 via the HKP-encapsulated method exhibited therapeutic efficacy in orthotopic xenografts. Our study presents a novel oncogenetic mechanism in which aberrant tuning of the chromatin state at specific chromosomal loci exposes factor-binding sites, leading to recruitment of trans-factor and activation of oncogenetic driver, thereby provide a novel alternative concept of chromatin dynamics in tumorigenesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 12
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Regulação Neoplásica da Expressão Gênica
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N-Acetilgalactosaminiltransferases
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RNA Longo não Codificante
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Carcinogênese
Limite:
Adult
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Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article