IGF2BP3-Mediated Stabilization of LINC01671 Promotes LDHA-Dependent Glycolysis and Immune Evasion in Ovarian Clear Cell Carcinoma

Abstract Ovarian clear cell carcinoma (OCCC) is a highly chemoresistant subtype of ovarian cancer with limited therapeutic options, while the mechanisms underlying metabolic reprogramming and immune evasion remain incompletely understood. In this study, integrative transcriptomic and metabolomic analyses identified the long non-coding RNA LINC01671 as markedly upregulated in OCCC and associated with poor clinical outcomes. Functional experiments demonstrated that LINC01671 promotes tumor growth, invasion, and aerobic glycolysis both in vitro and in vivo. Mechanistically, LINC01671 interacts with the RNA-binding protein IGF2BP3, which enhances its stability and facilitates upregulation of lactate dehydrogenase A (LDHA), thereby driving glycolytic reprogramming. Moreover, LINC01671 impaired MHC I–mediated antigen presentation and suppressed CD8⁺ T cell cytotoxicity, accompanied by reduced secretion of Granzyme B, IFN-γ, and Perforin, indicating a role in immune escape. Importantly, genetic depletion of LINC01671 or LDHA reversed these oncogenic and immunosuppressive phenotypes and sensitized tumor cells to T cell–mediated killing. Collectively, these findings identify an IGF2BP3–LINC01671–LDHA regulatory axis linking metabolic reprogramming to immune suppression and provide mechanistic insight into OCCC progression.