Ferroptosis induced by DCPS depletion diminishes hepatic metastasis in uveal melanoma.

Hepatic metastasis develops in ∼50% of uveal melanoma (UM) patients with scarcely effective treatment resulting in lethality. The underlying mechanism of liver metastasis remains elusive. Ferroptosis, a cell death form characterized by lipid peroxide, in cancer cells may decrease metastatic colonization. In the present study, we hypothesized that decapping scavenger enzymes (DCPS) impact ferroptosis by regulating mRNA decay during the metastatic colonization of UM cells to liver. We found that inhibition of DCPS by shRNA or RG3039 induced gene transcript alteration and ferroptosis through reducing the mRNA turnover of GLRX. Ferroptosis induced by DCPS inhibition eliminates cancer stem-like cells in UM. Inhibition of DCPS hampered the growth and proliferation both in vitro and in vivo. Furthermore, targeting DCPS diminished hepatic metastasis of UM cells. These findings may shed light on the understanding of DCPS-mediated pre-mRNA metabolic pathway in UM by which disseminated cells gain enhanced malignant features to promote hepatic metastasis, providing a rational target for metastatic colonization in UM.