IL-1β-mediated NF-κB signaling augments the osteosarcoma cell growth through modulating miR-376c/TGFA axis.

Overexpression of IL-1β, one of the most well-known pro-inflammatory cytokines, is related to a plenty of diseases including cancer. Diversion of microRNAs exposed to pro-inflammatory cytokines have been noted in cancer cells, however, their functions in inflammation stress are still to be further studied. In our previous study, we reported that miR-376c inhibited the growth of osteosarcoma (OS) cells by targeting TGFA. Here, we revealed that miR-376c was downregulated in OS tissues and cells while IL-1β, NF-κB and TGFA were upregulated in OS tissues and cells. IL-1β or NF-κB could promote the OS cells growth through inducing miR-376c expression and decreasing TGFA protein levels. Furthermore, forced expression of miR-376c restored the suppression of IL-1β on the OS cells. A decrease in miR-376c and an increase in TGFA depended on IL-1β-induced NF-κB protein level, which attenuates miR-376c expression upon IL-1β reduction. Taken together, our findings indicated that IL-1β augmented miR-376c-reduction to promote OS cell growth via upregulating NF-κB levels. Knock-down NF-κB suppressed the expression of TGFA. Enhanced TGFA upon IL-1β induction was attenuated by NF-κB inhibition. Hence, the regulation of IL-1β/NF-κB/miR-376c/TGFA signaling in OS might present a promising strategy for the treatment of OS.