SNHG7 is a lncRNA oncogene controlled by Insulin-like Growth Factor signaling through a negative feedback loop to tightly regulate proliferation.
Sci Rep
; 10(1): 8583, 2020 05 22.
Article
em En
| MEDLINE
| ID: mdl-32444795
ABSTRACT
Evidence suggests Insulin-like growth factor 1 (IGF1) signaling is involved in the initiation and progression of a subset of breast cancers by inducing cell proliferation and survival. Although the signaling cascade following IGF1 receptor activation is well-studied, the key elements of the transcriptional response governing IGF1's actions are not well understood. Recent studies reveal that the majority of the genome is transcribed and that there are more long non-coding RNAs (lncRNAs) than protein coding genes, several of which are dysregulated in human cancer. However, studies on the regulation and mechanism of action of these lncRNAs are in their infancy. Here we show that IGF1 alters the expression levels of a subset of lncRNAs. SNHG7, a member of the small nucleolar host gene family, is a highly-expressed lncRNA that is consistently and significantly down-regulated by IGF1 signaling by a post-transcriptional mechanism through the MAPK pathway. SNHG7 regulates proliferation of breast cancer cell lines in a dose-dependent manner, and silencing SNHG7 expression causes cell cycle arrest in G0/G1. Intriguingly, SNHG7 alters the expression of many IGF1 signaling intermediates and IGF1-regulated genes suggesting a feedback mechanism to tightly regulate the IGF1 response. Finally, we show in clinical data that SNHG7 is overexpressed in tumors of a subset of breast cancer patients and that these patients have lower disease-free survival than patients without elevated SNHG7 expression. We propose that SNHG7 is a lncRNA oncogene that is controlled by growth factor signaling in a feedback mechanism to prevent hyperproliferation, and that this regulation can be lost in the development or progression of breast cancer.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
/
2_ODS3
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6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Fator de Crescimento Insulin-Like I
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Biomarcadores Tumorais
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Proliferação de Células
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RNA Longo não Codificante
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2020
Tipo de documento:
Article