Function of HNRNPC in breast cancer cells by controlling the dsRNA-induced interferon response.
EMBO J
; 37(23)2018 12 03.
Article
en En
| MEDLINE
| ID: mdl-30158112
ABSTRACT
Elevated expression of RNA binding protein HNRNPC has been reported in cancer cells, while the essentialness and functions of HNRNPC in tumors were not clear. We showed that repression of HNRNPC in the breast cancer cells MCF7 and T47D inhibited cell proliferation and tumor growth. Our computational inference of the key pathways and extensive experimental investigations revealed that the cascade of interferon responses mediated by RIG-I was responsible for such tumor-inhibitory effect. Interestingly, repression of HNRNPC resulted in accumulation of endogenous double-stranded RNA (dsRNA), the binding ligand of RIG-I. These up-regulated dsRNA species were highly enriched by Alu sequences and mostly originated from pre-mRNA introns that harbor the known HNRNPC binding sites. Such source of dsRNA is different than the recently well-characterized endogenous retroviruses that encode dsRNA In summary, essentialness of HNRNPC in the breast cancer cells was attributed to its function in controlling the endogenous dsRNA and the down-stream interferon response. This is a novel extension from the previous understandings about HNRNPC in binding with introns and regulating RNA splicing.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
ARN Bicatenario
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ARN Neoplásico
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Regulación Neoplásica de la Expresión Génica
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Regulación hacia Arriba
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Interferones
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Ribonucleoproteína Heterogénea-Nuclear Grupo C
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Proteínas de Neoplasias
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
EMBO J
Año:
2018
Tipo del documento:
Article
País de afiliación:
China