lncRNA RP11-199F11.2 promotes high-grade serous ovarian cancer cell proliferation by regulating cuproptosis through FDX1.

To elucidate the expression characteristics of the long noncoding RNA RP11-199F11.2 (RP11) in high-grade serous ovarian cancer (HGSOC) and its potential mechanism of regulating cancer progression via the copper-death pathway, and to evaluate the therapeutic potential of the copper ion carrier ES-Cu. The interaction between RP11 and FDX1 was predicted via bioinformatics; the posttranscriptional inhibition of FDX1 by RP11 was verified via qRT‒PCR and Western blotting; the effects of RP11 knockdown/overexpression on proliferation were evaluated in in vitro and in subcutaneous xenograft cancer models; ES-Cu was used to induce copper death, and cell death patterns and circulating inflammatory cytokines were detected via flow cytometry and ELISA. RP11 was significantly highly expressed in HGSOC tissues and was positively correlated with FIGO stage and lymph node metastasis (P < 0.01). Mechanistically, bioinformatic analysis suggests that RP11 may binds the 3'-UTR of FDX1 to reduce its translation, thereby limiting copper death and increased cell proliferation. ES-Cu treatment restored FDX1 expression, re-activated copper death, and reduced tumour volume by 68% (P < 0.001) without detectable histological toxicity. RP11 is associated with inhibits copper death and modulation of local inflammatory milieu by suppressing FDX1, which may contribute to HGSOC progression. ES-Cu re-activates the FDX1-copper-death axis, providing a potential strategy for combining copper-death induction with immunomodulation in HGSOC.