REX1 promotes EMT-induced cell metastasis by activating the JAK2/STAT3-signaling pathway by targeting SOCS1 in cervical cancer

被引:71
作者
Zeng, Yu-Ting [1 ]
Liu, Xiao-Fang [2 ]
Yang, Wen-Ting [1 ]
Zheng, Peng-Sheng [1 ,2 ]
机构
[1] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Reprod Med, Xian 710061, Shaanxi, Peoples R China
[2] Minist Educ Peoples Republ China, Key Lab Environm & Genes Related Dis, Sect Canc Stem Cell Res, Xian 710061, Shaanxi, Peoples R China
基金
中国国家自然科学基金;
关键词
SIGNAL TRANSDUCER; DNA METHYLATION; GENE-EXPRESSION; YY1; PROTEIN; MARKER; CLASSIFICATION; ASSOCIATION; SUPPRESSOR; CARCINOMA;
D O I
10.1038/s41388-019-0906-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
ZFP42 zinc finger protein (REX1), a pluripotency marker in mouse pluripotent stem cells, has been identified as a tumor suppressor in several human cancers. However, the function of REX1 in cervical cancer remains unknown. Both IHC and western blot assays demonstrated that the expression of REX1 protein in cervical cancer tissue was much higher than that in normal cervical tissue. A xenograft assay showed that REX1 overexpression in SiHa and HeLa cells facilitated distant metastasis but did not significantly affect tumor formation in vivo. In addition, in vitro cell migration and invasion capabilities were also promoted by REX1. Mechanistically, REX1 overexpression induced epithelial-to-mesenchymal transition (EMT) by upregulating VIMENTIN and downregulating E-CADHERIN. Furthermore, the JAK2/STAT3-signaling pathway was activated in REX1-overexpressing cells, which also exhibited increased levels of p-STAT3 and p-JAK2, as well as downregulated expression of SOCS1, which is an inhibitor of the JAK2/STAT3-signaling pathway, at both the transcriptional and translational levels. A dual-luciferase reporter assay and qChIP assays confirmed that REX1 trans-suppressed the expression of SOCS1 by binding to two specific regions of the SOCS1 promoter. Therefore, all our data suggest that REX1 overexpression could play a crucial role in the metastasis and invasion of cervical cancer by upregulating the activity of the JAK2/STAT3 pathway by trans-suppressing SOCS1 expression.
引用
收藏
页码:6940 / 6957
页数:18
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