miR-21 Targets ASPP2 to Inhibit Apoptosis via CHOP-Mediated Signaling in -Infected Gastric Cancer Cells.

r () infection affects cell survival pathways, including apoptosis and proliferation in host cells, and disruption of this balance is the key event in the development of -induced gastric cancer (HPGC). infection induces alterations in microRNAs expression that may be involved in GC development. Bioinformatic analysis showed that microRNA-21 (miR-21) is significantly upregulated in HPGC. Furthermore, quantitative proteomics and in silico prediction were employed to identify potential targets of miR-21. Following functional enrichment and clustered interaction network analyses, five candidates of miR-21 targets, PDCD4, ASPP2, DAXX, PIK3R1, and MAP3K1, were found across three functional clusters in association with cell death and survival, cellular movement, and cellular growth and proliferation. ASPP2 is inhibited by -induced miR-21 overexpression. Moreover, ASPP2 levels are inversely correlated with miR-21 levels in HPGC tumor tissues. Thus, ASPP2 was identified as a miR-21 target in HPGC. Here, we observed that -induced ASPP2 suppression enhances resistance to apoptosis in GC cells using apoptosis assays. Using protein interaction network and coimmunoprecipitation assay, we identified CHOP as a direct mediator of the ASPP2 proapoptotic activity in -infected GC cells. Mechanistically, ASPP2 suppression promotes p300-mediated CHOP degradation, in turn inhibiting CHOP-mediated transcription of Noxa, Bak, and suppression of Bcl-2 to enact antiapoptosis in the GC cells after infection. Clinicopathological analysis revealed correlations between decreased ASPP2 expression and higher HPGC risk and poor prognosis. In summary, the discovery of -induced antiapoptosis via miR-21-mediated suppression of ASPP2/CHOP-mediated signaling provides a novel perspective for developing HPGC management and treatment.