GSE83634 Inhibition of NF- κB signaling by a novel siRNA sequence induces apoptosis and suppresses tumor growth in KRAS mutant colorectal cancer.

In this study, we aimed to discover an effective therapeutic microRNA (miRNA) that could target KRAS mutant CRC. For this purpose, we investigated the functional relevance of dysregulated miRNAs in KRAS mutant cancers. We transfected exogenous KRASG12V into human embryonic kidney 293 (HEK293) cells and human lung fibroblasts (MRC5) cells, and performed comprehensive microRNA expression profiling by microarray analysis. The results showed that 6 miRNAs are significantly upregulated in KRAS-transfected HEK293 and MRC5 cells. Among 6 miRNAs, we identified mature miRNA-29b-1-5p as potent growth inhibitor in CRC cell proliferation. However, miRNA-29b-1-5p was found to be a passenger strand with a star form (miRNA-29b-1-5p*), and did not function in CRC cells. Proliferation assay revealed that completely opposite complementary strand to miRNA-29b-1-5p possessed a potent anti-tumor effect. We named this novel anti-tumor siRNA sequence “MIRTX”. MIRTX induced apoptosis and significantly inhibited cell proliferation in KRAS mutant CRC in vitro. In addition, MIRTX suppressed NF-κB signaling pathway, which is downstream effector of KRAS in CRC. Furthermore, MIRTX directly targeted 3'-UTR of PIK3R1 and CXCR2 mRNA, and indirectly s uppressed KRAS itself. In vivo xenograft mouse models, systemic administration of MIRTX significantly inhibited the tumor growth with no particular toxicity, using carbonate apatite as a vehicle. These findings indicate that inhibition of NF-κB signaling b...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research