Fig. 3From: Synthetic lethal short hairpin RNA screening reveals that ring finger protein 183 confers resistance to trametinib in colorectal cancer cellsInduction of interleukin-8 (IL-8) transcription by RNF183 promoted cell proliferation and conferred resistance to trametinib. a mRNA levels of nuclear factor-kappa B (NF-κB) downstream genes in HCT116 cells transfected with small interfering RNAs (siRNAs) of RNF183 (siRNF183) or non-specific control (siNC) were detected by qPCR. IL-8 mRNA level is down-regulated in HCT116 cells transfected with siRNF183. b IL-8 mRNA levels are decreased in HT29 and HCT116 cells treated with 20 nmol/L trametinib for 48 h. c IL-8 protein levels are down-regulated in HT29 and HCT116 cells treated with 20 nmol/L trametinib for 48 h. Effects of trametinib treatment in combination with RNF183 overexpression or knockdown on IL-8 mRNA (d) and protein (e) levels in HT29 cells. f Effects of RNF183 overexpression with or without IL-8 knockdown on HT29 cell colony formation. g HT29 and HCT116 cells were transfected with siNC or IL-8-targeted siRNA (siIL-8) for 24 h; then the cells were treated with 20 nmol/L trametinib for an additional 72 h, and the cell viability was measured with MTT assay. All experiments were repeated at least three times, and data are presented as mean ± SD. SELE selectin E, PLAU plasminogen activator urokinase, ICAM1 intercellular adhesion molecule 1, CXCR4 C-X-C motif chemokine receptor 4, IL-6 interleukin-6, MMP9 matrix metallopeptidase 9. *P < 0.05, **P < 0.01, ***P < 0.001Back to article page