Heterozygous deletion-mediated TRIM3 downregulation led to NF-κB constitutive activation through disruption of the NF-κB-IκB-α negative feedback loop and enhancement of the p65 DNA-binding affinity and transcriptional activity via promoting symmetrical dimethylarginine modification of NF-κB/p65 at Arg30 and Arg35, which consequently promoted lymphatic metastasis of esophageal squamous cell carcinoma (ESCC) cells.
To explore the role of NF-κB signaling pathway in ESCC, RNA interference (RNAi) was used to knockdown the NF-κB p65 protein level in the ESCC cells and nude mice.
Reverse transcription-polymerase chain reaction results showed the constitutive expressions of p50, p65 and IkappaBalpha mRNA in the two ESCC cell lines.
Both p65 siRNA and curcumin mediated suppression of activation of the NF-κB signaling pathway via inhibition of the expression of p65 or IκBα phosphorylation in ESCC cell lines.