Characterization of super-enhancer-associated functional lncRNAs acting as ceRNAs in ESCC.
Mol Oncol
; 14(9): 2203-2230, 2020 09.
Article
en En
| MEDLINE
| ID: mdl-32460441
ABSTRACT
Long noncoding RNAs (lncRNAs) have important regulatory roles in cancer biology. Although some lncRNAs have well-characterized functions, the vast majority of this class of molecules remains functionally uncharacterized. To systematically pinpoint functional lncRNAs, a computational approach was proposed for identification of lncRNA-mediated competing endogenous RNAs (ceRNAs) through combining global and local regulatory direction consistency of expression. Using esophageal squamous cell carcinoma (ESCC) as model, we further identified many known and novel functional lncRNAs acting as ceRNAs (ce-lncRNAs). We found that most of them significantly regulated the expression of cancer-related hallmark genes. These ce-lncRNAs were significantly regulated by enhancers, especially super-enhancers (SEs). Landscape analyses for lncRNAs further identified SE-associated functional ce-lncRNAs in ESCC, such as HOTAIR, XIST, SNHG5, and LINC00094. THZ1, a specific CDK7 inhibitor, can result in global transcriptional downregulation of SE-associated ce-lncRNAs. We further demonstrate that a SE-associated ce-lncRNA, LINC00094 can be activated by transcription factors TCF3 and KLF5 through binding to SE regions and promoted ESCC cancer cell growth. THZ1 downregulated expression of LINC00094 through inhibiting TCF3 and KLF5. Our data demonstrated the important roles of SE-associated ce-lncRNAs in ESCC oncogenesis and might serve as targets for ESCC diagnosis and therapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Esofágicas
/
Regulación Neoplásica de la Expresión Génica
/
Elementos de Facilitación Genéticos
/
ARN Largo no Codificante
/
Carcinoma de Células Escamosas de Esófago
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Oncol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2020
Tipo del documento:
Article
País de afiliación:
China