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Knockdown of IGF-1R Triggers Viral RNA Sensor MDA5- and RIG-I-Mediated Mitochondrial Apoptosis in Colonic Cancer Cells.
Wang, Shu-Qing; Yang, Xiang-Yu; Yu, Xin-Feng; Cui, Shu-Xiang; Qu, Xian-Jun.
Afiliación
  • Wang SQ; Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
  • Yang XY; Department of Stomatology, Aerospace Center Hospital, Haidian District, Beijing, China.
  • Yu XF; Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
  • Cui SX; Beijing Key Laboratory of Environmental Toxicology, Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, China. Electronic address: sxccui@ccmu.edu.cn.
  • Qu XJ; Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. Electronic address: quxj@ccmu.edu.cn.
Mol Ther Nucleic Acids ; 16: 105-117, 2019 Jun 07.
Article en En | MEDLINE | ID: mdl-30861413
ABSTRACT
The important role of insulin-like growth factor-1 receptor (IGF-1R) in tumorigenesis has been well established. The classical model involves IGF-1R binding to IGF-1/2, the following activation of PI3K-Akt-signaling cascades, driving cell proliferation and apoptosis inhibition. Here we report a new signal transduction pathway of IGF-1R in the intestinal epithelium. Using heterozygous knockout mice (Igf1r+/-), we analyzed the expressions of viral RNA sensors MDA5 and RIG-I in the intestinal epithelium. Igf1r+/- mice exhibited higher MDA5 and RIG-I than wild-type (WT) mice, indicating that knockdown of IGF-1R could trigger MDA5 and RIG-I. IGF-1R knockdown-triggered MDA5 and RIG-I were further investigated in human colonic cancer cells. Increased MDA5 and RIG-I were clearly seen in the cytoplasm in cancer cells as well as normal human colonic cells with silenced IGF-1R. Notably, the upregulations of MDA5 and RIG-I was not affected by blockage of the PI3K-Akt pathway with LY294002. These results suggested a new signal transduction pathway of IGF-1R. Importantly, IGF-1R knockdown-triggered MDA5 and RIG-I resulted in colorectal cancer apoptosis through activation of the mitochondrial pathway. These in vitro observations were evidenced in the azoxymethane (AOM)-dextran sulfate sodium (DSS) colorectal cancer model of mice. In conclusion, knockdown of IGF-1R triggers viral RNA sensor MDA5- and RIG-I-mediated mitochondrial apoptosis in cancer cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Ther Nucleic Acids Año: 2019 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Ther Nucleic Acids Año: 2019 Tipo del documento: Article País de afiliación: China