Downregulation of TNFR2 decreases survival gene expression, promotes apoptosis and affects the cell cycle of gastric cancer cells

Figure 6 Schematic comparison of the tumour necrosis factor-α signalling pathway and cell fate in nonsilenced AGS, shTNFR1 and shTNFR2 cells with downregulation after treatment with Helicobacter pylori extract. After the tumour necrosis factor (TNF)-α/TNFR1 interaction, TRADD, RIP1, TRAF2 and cellular inhibitor of apoptosis proteins are recruited, which results in nuclear factor-kappaB (NF-κB) activation and transcription of prosurvival and antiapoptotic genes, such as CFLIP, that inhibit the activity of the death-inducing signalling complex, which is formed after dissociation between TRADD and TNFR1. As with TNFR1, TNFR2 stimulation leads to NF-κB activation and cell survival; A: Treatment with Helicobacter pylori (H. pylori) extract resulted in increased expression of TNFR1, NFKB1, NFKB2 and CFLIP mRNAs in nonsilenced AGS cells. Therefore, the cell survival pathway is activated due to NF-kB activation (red ellipse) through the TNFR1-TNF signalling pathway with consequent production of the antiapoptotic CFLIP; B: In shTNFR1-H. pylori extract cells, TNFR1 downregulation resulted in decreased expression of TRADD and CFLIP mRNAs; however, it did not change cell fate; C: In shTNFR2-H. pylori extract cells, TNFR2 downregulation decreased the expression of TRAF2 and TRADD, decreased NFKB1, CFLIP and TNFR1 expression, and upregulated miR-19a and miR-34a. This led to an increase in apoptosis, impairing cell survival due to arrest in the G1/S transition phase.