TRIM46 promotes chemoresistance of ovarian cancer via activating PHLPP2/PI3K/AKT pathway

Ovarian cancer is one of the most common and lethal malignancy tumors in women. Chemoresistance is one of the main reasons for ovarian cancer relapsing. Understanding the regulatory mechanisms of chemoresistance generation is critical to develop novel therapeutic strategies. Here, we found that TRIM46 was upregulated in ovarian cancer cells and tissues with chemoresistance and associated with poor outcomes. Functional assays showed that TRIM46 promoted cisplatin (CDDP) chemoresistance. Furthermore, TRIM46 interacts with PI3K/AKT pathway inactivator pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) and downregulated PHLPP2 level. Treating with PI3K/AKT pathway inhibitor significantly reversed the effects of TRIM46-overexpressing on chemoresistance. In summary, our study reveals that TRIM46 promoted chemoresistance via downregulating PHLPP2, leading to activating PI3K/AKT pathway. This study provides a novel potential target for ovarian cancer therapy.