Liang Peng, Limei Liu, Ling Xu, Jie Chen, Xiaohui Wang, Meihua Zhang, Yilong Ge
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引用次数: 0
摘要
卵巢癌是女性最常见、最致命的恶性肿瘤之一。化疗耐药是卵巢癌复发的主要原因之一。了解化疗耐药产生的调控机制对于开发新的治疗策略至关重要。在这里，我们发现TRIM46在化疗耐药的卵巢癌细胞和组织中上调，并与不良预后相关。功能分析显示TRIM46促进顺铂（CDDP）化疗耐药。此外，TRIM46与PI3K/AKT通路失活因子pleckstrin同源结构域富亮氨酸重复蛋白磷酸酶2 （leucine-rich repeat protein phosphatase 2, PHLPP2）相互作用，下调PHLPP2水平。用PI3K/AKT通路抑制剂治疗可显著逆转trim46过表达对化疗耐药的影响。综上所述，我们的研究表明TRIM46通过下调PHLPP2促进化疗耐药，从而激活PI3K/AKT通路。本研究为卵巢癌治疗提供了新的潜在靶点。
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.
期刊介绍：
Published since 1929, Biochemistry and Cell Biology explores every aspect of general biochemistry and includes up-to-date coverage of experimental research into cellular and molecular biology in eukaryotes, as well as review articles on topics of current interest and notes contributed by recognized international experts. Special issues each year are dedicated to expanding new areas of research in biochemistry and cell biology.
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