Genome-wide RNAi screening identifies TMIGD3 isoform1 as a suppressor of NF-κB and osteosarcoma progression.
Nat Commun
; 7: 13561, 2016 11 25.
Article
em En
| MEDLINE
| ID: mdl-27886186
ABSTRACT
The ability of cancer cells to survive and grow in anchorage- and serum-independent conditions is well correlated with their aggressiveness. Here, using a human whole-genome shRNA library, we identify TMIGD3 isoform1 (i1) as a factor that suppresses this ability in osteosarcoma (OS) cells, mainly by inhibiting NF-κB activity. Knockdown of TMIGD3 increases proliferation, tumour formation and metastasis of OS cells. Overexpression of TMIGD3 isoform1 (i1), but not isoform3 (i3) which shares a common C-terminal region, suppresses these malignant properties. Adenosine A3 receptor (A3AR) having an identical N-terminal region shows similar biological profiles to TMIGD3 i1. Protein expression of TMIGD3 and A3AR is lower in human OS tissues than normal tissues. Mechanistically, TMIGD3 i1 and A3AR commonly inhibit the PKA-Akt-NF-κB axis. However, TMIGD3 i1 only partially rescues phenotypes induced by A3AR knockdown, suggesting the presence of distinct pathways. Our findings reveal an unappreciated role for TMIGD3 i1 as a suppressor of NF-κB activity and OS progression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ósseas
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Glicoproteínas de Membrana
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Osteossarcoma
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NF-kappa B
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Receptor A3 de Adenosina
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Neoplasias Pulmonares
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Proteínas de Membrana
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Screening_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2016
Tipo de documento:
Article