Super-enhancer-associated TMEM44-AS1 aggravated glioma progression by forming a positive feedback loop with Myc.
J Exp Clin Cancer Res
; 40(1): 337, 2021 Oct 25.
Article
de En
| MEDLINE
| ID: mdl-34696771
ABSTRACT
BACKGROUND:
Long non-coding RNAs (lncRNAs) have been considered as one type of gene expression regulator for cancer development, but it is not clear how these are regulated. This study aimed to identify a specific lncRNA that promotes glioma progression.METHODS:
RNA sequencing (RNA-seq) and quantitative real-time PCR were performed to screen differentially expressed genes. CCK-8, transwell migration, invasion assays, and a mouse xenograft model were performed to determine the functions of TMEM44-AS1. Co-IP, ChIP, Dual-luciferase reporter assays, RNA pulldown, and RNA immunoprecipitation assays were performed to study the molecular mechanism of TMEM44-AS1 and the downstream target.RESULTS:
We identified a novel lncRNA TMEM44-AS1, which was aberrantly expressed in glioma tissues, and that increased TMEM44-AS1 expression was correlated with malignant progression and poor survival for patients with glioma. Expression of TMEM44-AS1 increased the proliferation, colony formation, migration, and invasion of glioma cells. Knockdown of TMEM44-AS1 in glioma cells reduced cell proliferation, colony formation, migration and invasion, and tumor growth in a nude mouse xenograft model. Mechanistically, TMEM44-AS1 is directly bound to the SerpinB3, and sequentially activated Myc and EGR1/IL-6 signaling; Myc transcriptionally induced TMEM44-AS1 and directly bound to the promoter and super-enhancer of TMEM44-AS1, thus forming a positive feedback loop with TMEM44-AS. Further studies demonstrated that Myc interacts with MED1 regulates the super-enhancer of TMEM44-AS1. More importantly, a novel small-molecule Myc inhibitor, Myci975, alleviated TMEM44-AS1-promoted the growth of glioma cells.CONCLUSIONS:
Our study implicates a crucial role of the TMEM44-AS1-Myc axis in glioma progression and provides a possible anti-glioma therapeutic agent.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Régulation de l'expression des gènes tumoraux
/
Gènes myc
/
Éléments activateurs (génétique)
/
Épistasie
/
ARN long non codant
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Gliome
Type d'étude:
Prognostic_studies
/
Risk_factors_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
J Exp Clin Cancer Res
Année:
2021
Type de document:
Article
Pays d'affiliation:
Chine