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Esculetin inhibits endometrial cancer proliferation and promotes apoptosis via hnRNPA1 to downregulate BCLXL and XIAP
Cancer Letters ( IF 9.1 ) Pub Date : 2021-09-01 , DOI: 10.1016/j.canlet.2021.08.039
Ruqi Jiang 1 , Guifeng Su 1 , Xi Chen 1 , Shuo Chen 1 , Qianhui Li 1 , Bumin Xie 1 , Yang Zhao 1
Affiliation  

Endometrial cancer represents one of the most common gynecological tumors in the world. Advanced and relapsed patients rely on drug therapy. Therefore, it is extremely important to seek more effective targeted drugs. This study found that esculetin has an anti-tumor effect on endometrial cancer through cellular proliferation and apoptosis. At the same time, its anti-tumor effect has also been verified in human endometrial cancer xenograft models in nude mice. Western blot results showed that BCLXL, XIAP, and pAKT protein expression level were down-regulated. A pulldown experiment and LC-MS/MS analysis technology revealed that esculetin targets the hnRNPA1 protein. Cellular proliferation experiments following si-hnRNPA1 transfection verified the tumor-promoting effect of hnRNPA1 in endometrial cancer cells. Nuclear and cytoplasmic separation experiment demonstrated esculetin affecting the export of the hnRNPA1/mRNA complex from the nucleus into the cytoplasm. Thus, esculetin targets hnRNPA1, thereby downregulates BCLXL and XIAP mRNA transcription and translation, resulting in apoptosis and an arrest in proliferation.



中文翻译:


Esculetin 通过 hnRNPA1 下调 BCLXL 和 XIAP 抑制子宫内膜癌增殖并促进细胞凋亡



子宫内膜癌是世界上最常见的妇科肿瘤之一。晚期和复发患者依赖药物治疗。因此,寻找更有效的靶向药物显得极为重要。本研究发现七叶亭通过细胞增殖和凋亡对子宫内膜癌具有抗肿瘤作用。同时,其抗肿瘤作用也在人子宫内膜癌裸鼠异种移植模型中得到验证。 Western blot结果显示BCLXL、XIAP和pAKT蛋白表达水平下调。 Pulldown 实验和 LC-MS/MS 分析技术表明 esculetin 靶向 hnRNPA1 蛋白。 si-hnRNPA1转染后的细胞增殖实验验证了hnRNPA1在子宫内膜癌细胞中的促肿瘤作用。核和细胞质分离实验证明七叶亭影响 hnRNPA1/mRNA 复合物从细胞核输出到细胞质。因此,七叶亭靶向 hnRNPA1,从而下调 BCLXL 和 XIAP mRNA 转录和翻译,导致细胞凋亡和增殖停滞。

更新日期:2021-09-01
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