Long non-coding RNA HCP5 accelerated malignant progression of ovarian cancer by inhibiting ferroptosis through interaction with polypyrimidine tract binding protein 1.

BACKGROUND: Ovarian cancer (OVCA) is the third most common gynaecological malignancy worldwide. Long non-coding RNA (LncRNA) HCP5 and polypyrimidine tract binding protein 1 (PTBP1) involved in regulating tumors, however, with undefined mechanism in OVCA. METHODS: After validating lentiviral transfection efficiency, OVCA mouse models were constructed by intraperitoneal injection of ID8-Luc cells for 8 weeks, with sh-lncRNA HCP5, oe-PTBP1, and ferroptosis agonist Erastin treatment. In vivo imaging, tumor metastasis, immunohistochemistry, HE, and TUNEL staining were performed. Human ovarian adenocarcinoma cell SKOV3 cells underwent the same grouping. Interaction between lncRNA HCP5 and PTBP1 was examined using RNA immunoprecipitation and RNA pull-down assay. CCK8, flow cytometry, transmission electron microscopy, biochemical kits, qRT-PCR, and Western blot were performed. RESULTS: In OVCA mice, sh-lncRNA HCP5 inhibited tumor growth and increased tumor tissue pathological damage and apoptosis, with lower PTBP1, Ki67, and B-cell lymphoma-2 (Bcl-2) expression, and higher Bcl-2 associated X and caspase-3 expression. Meanwhile, sh-lncRNA HCP5 induced ferroptosis, with reduced glutathione peroxidase 4, glutathione, and recombinant solute carrier family 7, member 11 expression, and elevated malondialdehyde, lipid peroxides, 4-hydroxynonenoic acid, acyl-CoA synthetase long chain family member 4, and transferrin receptor protein expression. These effects were reversed by oe-PTBP1, and Erastin weakened the pro-tumor role of oe-PTBP1, which were also observed in SKOV3 cells. Additionally, in vitro, lncRNA HCP5 was confirmed to bind to PTBP1, and sh-lncRNA HCP5 reduced cell viability and enhanced reactive oxygen species. CONCLUSION: LncRNA HCP5 may promote OVCA progression by inhibiting ferroptosis through interaction with PTBP1, providing new targets in OVCA treatment.