Qiu Ping, Jie Youkun, Ma Cheng, Chen Huifeng, Qin Yunna, Tu Kaijia, Wang Liqun, Zhang Ziyu
Department of Pathology, Jiangxi Maternal & Child Health Hospital, 330006, Nanchang, Jiangxi, P. R. China.
Department of Reproductive Health, Jiangxi Maternal & Child Health Hospital, 330006, Nanchang, Jiangxi, P. R. China.
Cell Death Discov. 2022 Jun 7;8(1):276. doi: 10.1038/s41420-022-01072-8.
As a molecular marker of the female reproductive system, Paired Box 8 is widely used in pathological diagnosis of gynecological tumors, but it is not clear whether its expression level is related to the development of uterine corpus endometrial carcinoma and molecular subtype classifications. Here, we show that PAX8 is up-regulated in TP53 mutation category of UCEC, which is result from the low methylation level of PAX8 in UCEC. We have identified that genes connected to ribosome, lysosome, ribosome biogenesis and cell cycle as PAX8 targets and demonstrate that modulation of the PAX8-DDX5 interaction influences c-MYC related cell cycle and cell growth. Our work defines DDX5 as a critical PAX8 co-factor, places the PAX8-DDX5 interaction in biological context, and highlights PAX8 as a key point for development of novel anti-MYC therapies in TP53-mutation UCEC.
作为女性生殖系统的分子标志物，配对盒8（Paired Box 8）在妇科肿瘤的病理诊断中被广泛应用，但尚不清楚其表达水平是否与子宫内膜癌的发生发展及分子亚型分类相关。在此，我们发现PAX8在子宫内膜癌（UCEC）的TP53突变类型中上调，这是由于UCEC中PAX8的低甲基化水平所致。我们已确定与核糖体、溶酶体、核糖体生物发生和细胞周期相关的基因是PAX8的靶点，并证明PAX8与DDX5相互作用的调节会影响c-MYC相关的细胞周期和细胞生长。我们的工作将DDX5定义为关键的PAX8辅因子，将PAX8与DDX5的相互作用置于生物学背景中，并突出了PAX8作为TP53突变型UCEC新型抗MYC疗法开发关键点的地位。
