NF-kappaB-dependent microRNA-425 upregulation promotes gastric cancer cell growth by targeting PTEN upon IL-1ß induction.

ABSTRACT

Overexpression of the proinflammatory cytokine IL-1ß is associated with diverse diseases, including cancer. Alteration of microRNAs has been observed in cancer cells exposed to proinflammatory cytokines, yet their function in inflammation stress remains elusive. Here, we show that IL-1ß induces the upregulation of miR-425, which negatively regulates phosphatase and tensin homolog expression by targeting its 3' UTR. An increase in miR-425 depends on IL-1ß-induced NF-kappaB activation, which enhances miR-425 gene transcription upon IL-1ß induction. Consequently, repression of phosphatase and tensin homolog by miR-425 promotes gastric cancer cell proliferation, which is required to protect cells from cisplatin-induced apoptosis. Taken together, our data support a critical role for NF-kappaB-dependent upregulation of miR-425, which represents a new pathway for the repression of phosphatase and tensin homolog activation and the promotion of cell survival upon IL-1ß induction.