LIN28B Promotes Cancer Progression by Regulating the Warburg Effect via PFKP in Epithelial Ovarian Cancer

Background: Ovarian cancer (OC) is one of the most aggressive and fatal malignancies in women, especially high-grade serous ovarian cancer, which has a mortality rate of 90% and a five-year survival rate of only 31%. LIN28B is an evolutionarily RNA-binding protein that is aberrantly activated in cancer, leading to the dysregulation of posttranscriptional gene expression. However, the possible roles and mechanisms of LIN28B in OC have not been fully explored. Results: Expression of LIN28B was upregulated in ovarian cancer and significantly correlated with poor prognosis. Cox analysis revealed that high expression of LIN28B was an independent predictor of overall survival among late-stage OC patients. Functional experiments demonstrated that LIN28B overexpression promoted ovarian cancer cell proliferation and invasion, while knockout did the opposite. Xenograft tumour model indicated that overexpressing LIN28B promoted tumour growth in mice. Metabolic analysis revealed that LIN28B modulated mitochondrial respiration and glycolytic processes. Mechanistically, LIN28B bound and stabilized PFKP mRNA to facilitate the Warburg effect, rescue functional and metabolic assays further confirmed this phenomenon. Conclusions: Our study reveals a novel pathway independent of the LIN28/let-7 axis by which LIN28B promotes ovarian cancer progression by stabilizing PFKP mRNA to mediate the Warburg effect. LIN28B may be used as a prognostic predictor and a potential therapeutic target in ovarian cancer.