卵巢癌SOX4介导TGF-β1诱导的上皮间质转化对侵袭转移能力的影响

doi:10.3969/j.issn.1006-7795.2022.03.002

首都医科大学学报 ›› 2022, Vol. 43 ›› Issue (3): 336-342.doi: 10.3969/j.issn.1006-7795.2022.03.002

• 更年期妇科内分泌与生育力保护 • 上一篇下一篇

卵巢癌SOX4介导TGF-β1诱导的上皮间质转化对侵袭转移能力的影响

刘群^1,2, 李丽娜³, 刘健³, 苗劲蔚^2*

1.首都医科大学附属北京安贞医院妇产科,北京 100029;
2.首都医科大学附属北京妇产医院/北京妇幼保健院妇瘤科,北京 100006;
3.首都医科大学附属北京朝阳医院医学研究中心,北京 100020

收稿日期:2021-02-27 出版日期:2022-06-21 发布日期:2022-06-01
基金资助:
国家自然科学基金(82002754),北京市自然科学基金(7162063)。

SOX4 mediates TGF-β1 induced epithelial-mesenchymal transition to promote invasion and metastasis of ovarian cancer

Liu Qun^1,2, Li Lina³, Liu Jian³, Miao Jinwei^2*

1. Department of Obstetrics and Gynecology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China;
2. Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing 100006, China;
3. Department of Oncology and Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China

Received:2021-02-27 Online:2022-06-21 Published:2022-06-01
Contact: *E-mail:jinweimiao@ccmu.edu.cn
Supported by:
National Natural Science Foundation of China (82002754),Natural Science Foundation of Beijing (7162063).

摘要/Abstract

摘要： 目的探讨SOX4(SRY-related HMG-box4)在卵巢癌中的表达、调控及其对转化生长因子-β1(transforming growth factor-β1,TGF-β1)诱导卵巢癌上皮间质转化(epithelial-mesenchymal transition, EMT)能力的影响。方法通过对TCGA、GEO等数据库中卵巢癌样本表达谱数据进行分析,探讨SOX4在卵巢癌中的表达情况,及其与EMT相关标志物的相关性。利用shRNA技术敲降卵巢癌SKOV3细胞系中SOX4的表达;利用Western blotting和qRT-PCR技术检测SOX4敲降对上皮标志物ZO1及间质标志物Vimentin和Slug表达的影响;利用Transwell技术检测SOX4敲降对卵巢癌细胞迁移和侵袭能力的影响;使用TGF-β1(10 ng/mL)处理SKOV3细胞72 h,然后通过 Western blotting 和qRT-PCR技术,检测TGF-β1对SOX4表达的调控情况,以及SOX4敲除对TGF-β1诱导EMT能力的影响。结果 SOX4在卵巢癌中的表达显著上调,并与EMT间质标志物呈显著正相关;敲除SOX4可显著下调卵巢癌SKOV3细胞的EMT水平及其侵袭转移能力;TGF-β1可显著上调卵巢癌SKOV3细胞中SOX4的表达水平,而SOX4敲除可显著抑制TGF-β1诱导卵巢癌EMT的能力。结论 SOX4在卵巢癌中表达上调,通过激活EMT促进其侵袭转移能力;并且,作为TGF-β1下游靶蛋白,SOX4介导了TGF-β1对卵巢癌EMT的诱导过程。因此,SOX4是一个干预卵巢癌转移的重要靶点。

关键词: 卵巢癌, 转移, SOX4, 转化生长因子β1(TGF-β1), 上皮间质转化

Abstract: Objective To investigate the expression and regulation of SOX4 (SRY-related HMG-box4) in ovarian cancer and its effect on transforming growth factor-β1(TGF-β1) induction of epithelial-mesenchymal transition (EMT). Methods The mRNA expression profile of ovarian cancer sample from TCGA, GEO databases were analyzed to assess the expression of SOX4 and its correlation with EMT markers in ovarian cancer; The expression of SOX4 in ovarian cancer SKOV3 cell line was knocked down by shRNA technology. Western blotting and qRT-PCR were used to detect the effects of SOX4 knockdown on epithelial marker ZO1 and mesenchymal markers Vimentin and Slug. Transwell technique was used to detect the effect of SOX4 knockdown on the migration and invasion abilities of ovarian cancer cells. To detect the regulation of TGF-β1 on SOX4 and the effect of SOX4 knockdown on TGF-β1 induced EMT, SKOV3 cells were treated with 10 ng/mL TGF-β1 for 72 h, followed by Western blotting and qRT-PCR assays. Results SOX4 expression was significantly up-regulated in ovarian cancer, and positively correlated with expression of mesenchymal markers. Deletion of SOX4 significantly suppressed EMT and thus inhibited migration and invasion of SKOV3 cells. SOX4 was induced by TGF-β1, and SOX4 knockdown significantly inhibited the ability of TGF-β1 to induce EMT in ovarian cancer. Conclusion Upregulation of SOX4 promoted migration and invasion in ovarian cancer by activating EMT. Moreover, as a downstream target of TGF-β1, SOX4 mediated TGF-β1-induced EMT in ovarian cancer.

Key words: ovarian cancer, metastasis, SOX4, transforming growth factor-β1(TGF-β1), epithelial-mesenchymal transition (EMT)

中图分类号:

R737.31

刘群, 李丽娜, 刘健, 苗劲蔚. 卵巢癌SOX4介导TGF-β1诱导的上皮间质转化对侵袭转移能力的影响[J]. 首都医科大学学报, 2022, 43(3): 336-342.

Liu Qun, Li Lina, Liu Jian, Miao Jinwei. SOX4 mediates TGF-β1 induced epithelial-mesenchymal transition to promote invasion and metastasis of ovarian cancer[J]. Journal of Capital Medical University, 2022, 43(3): 336-342.

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卵巢癌SOX4介导TGF-β1诱导的上皮间质转化对侵袭转移能力的影响

SOX4 mediates TGF-β1 induced epithelial-mesenchymal transition to promote invasion and metastasis of ovarian cancer

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