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Series GSE122534 Query DataSets for GSE122534
Status Public on Nov 30, 2019
Title Knockdown IGF-1R triggers viral RNA sensors MDA5- and RIG-1-mediated the mitochondrial apoptosis in colonic cancer cells
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The important role of IGF-1R in cancers has been well established. Classical model involves IGF-1/2 binding to IGF-1R, following activation of the PI3K/Akt pathway, thereby promoting cell proliferation, apoptosis inhibition and treatment resistance. While IGF-1R has become a promising target for cancer therapy, clinical disclosures subsequently have been less encouraging. The question is whether targeting IGF/IGF-1R still holds therapeutic potential. Here we show a novel mechanism that knockdown IGF-1R surprisingly triggers cytoplasmic viral RNA sensors MDA5 and RIG-1, leading to mitochondrial apoptosis in cancer. We analyzed MDA5 and RIG-1 in the intestinal epithelium of IGF-1R knockdown mice. Igf1r+/- mice demonstrated higher MDA5 and RIG-1 than WT mice. IGF-1R knockdown-triggered MDA5 and RIG-1 was further analyzed in human cancer and normal cells. Increased MDA5 and RIG-1 were clearly seen in the cytoplasm identified by immunofluoresce in the cells silenced IGF-1R. Block off IGF-1R downstream PI3K/Akt did not impact on MDA5 and RIG-1 expression. IGF-1R knockdown-triggered MDA5 and RIG-1 and their signaling pathways were similar to those of viral RNA mimetic poly(I:C) had. IGF-1R knockdown-triggered MDA5 and RIG-1 led to cancer apoptosis through activation of the mitochondrial pathway. In vivo assay, Igf1r+/- mice strongly resisted AOM-induced colonic tumorigenesis through triggering MDA¬5- and RIG-1-mediated apoptosis. Notably, RIG-I and MDA5-mediated proapoptotic signaling pathway is preferential active in cancer cells. These data suggest that targeting IGF-1R-triggered MDA5 and RIG-1 might have therapeutic potential for cancer treatment.
Overall design Examination of 2 different histone modifications in 2 cell types.
Contributor(s) Wang SQ, Yang XY
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Submission date Nov 14, 2018
Last update date Nov 30, 2019
Contact name shuqing wang
Organization name Capital Medical University
Street address No.10, You An Men Wai, Fengtai.
City Beijing
ZIP/Postal code 100069
Country China
Platforms (1)
GPL17303 Ion Torrent Proton (Homo sapiens)
Samples (2)
GSM3473350 HT-29
GSM3473351 HT-29-siIGF-1R
BioProject PRJNA505500
SRA SRP168619

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Supplementary file Size Download File type/resource
GSE122534_All_Counts.xls.gz 1.5 Mb (ftp)(http) XLS
GSE122534_All_RPKM.xls.gz 1.9 Mb (ftp)(http) XLS
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