Hypoxia-induced RNASEH2A limits activation of cGAS-STING signaling in HCC and predicts poor prognosis.
Tumori
; 108(1): 63-76, 2022 Feb.
Article
em En
| MEDLINE
| ID: mdl-34165025
ABSTRACT
BACKGROUND:
Hypoxia is a hallmark of solid cancers, including hepatocellular carcinoma (HCC). There is scarce information about how hypoxia avoids immunologic stress and maintains a cancer-promoting microenvironment.METHODS:
The Cancer Genome Atlas, RNA-seq data, and Oncomine database were used to discover the correlation of RNASEH2A with tumor progression; then expression of RNASEH2A mRNA and protein were detected in HCC tissues and cells subjected to hypoxia or with the treatment of CoCl2 via real-time quantitative polymerase chain reaction and immunochemistry assays. Finally, the effect of RNASEH2A on cell proliferation and the involved signaling pathway was explored further.RESULTS:
RNASEH2A was positively correlated with tumor grade, size, vascular invasion, and poor prognosis. The expression of RNASEH2A mRNA and protein were increased and dependent on hypoxia-inducible factor 2α in HCC tissues and cell lines. Knockout of RNASEH2A in HCC cells greatly reduced cell proliferation and induced the transcription of multiple cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) targeted type 1 interferon-related genes, including IFIT1, USP18, and CXCL10, which suggests knockout of RNASEH2A may produce immunologic stress and tumor suppressive effects.CONCLUSIONS:
RNASEH2A plays a critical role and potentially predicts patient outcomes in HCC, which uncovers a new mechanism that RNASEH2A contributes to limit immunologic stress of cancer cells in the context of hypoxia.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
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Ribonuclease H
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Neoplasias Hepáticas
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Proteínas de Membrana
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Nucleotidiltransferases
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Tumori
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China