New STAT3-FOXL2 pathway and its function in cancer cells
New STAT3-FOXL2 pathway and its function in cancer cells
复制标题
新的STAT3-FOXL2通路及其在癌细胞中的功能
DOI：
10.1186/s12860-019-0206-3
复制
发表时间：
2019-06-20
影响因子：
2.8
通讯作者：
Cheng, Min
中科院分区：
文献类型：
--
作者：
Han, Yangyang;Wu, Jun;Cheng, Min
背景叉头转录因子（FOXL2）在眼睑裂-下垂-内眦赘皮反位综合征（BPES）、性别决定、卵巢生长发育以及细胞周期调节中发挥着至关重要的作用。新兴的研究集中在 FOXL2 的下游靶点，而对其上游调控知之甚少。 结果在本研究中，我们使用 EMSA 和 ChIP 证明 FOXL2 可以在癌细胞中受到 STAT3 的调控，并且 STAT3 在 5'-GCCTGATGTTTGTCTTCCCAGTCTGTGGCAA-3' 位点与 FOXL2 结合。我们进一步发现STAT3或FOXL2的敲低可以显着诱导癌细胞凋亡，表明这两个基因在癌细胞生长和凋亡中的重要性。我们的数据还表明，细胞凋亡率增加可能是由凋亡相关基因的变化引起的，如TNF、TRAIL和GnRHR。结论本研究提出了一种新的FOXL2上游调节因子，并证明这种新的STAT3-FOXL2通路在HeLaHeLa细胞凋亡中具有重要作用，为FOXL2靶向癌症预防和治疗提供了新的见解。
BackgroundThe forkhead transcription factor (FOXL2) plays a crucial role in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), sex determination, ovary growth and development, and cell cycle regulation. Emerging investigations have focused on the downstream targets of FOXL2, while little is known about its upstream regulation.ResultsIn this study, we show that FOXL2 could be regulated by STAT3 in cancer cells and that STAT3 binds to FOXL2 at the 5′- GCCTGATGTTTGTCTTCCCAGTCTGTGGCAA-3′ site using EMSA and ChIP. We further found that knockdown of STAT3 or FOXL2 could significantly induce cancer cell apoptosis, indicating the importance of these two genes in cancer cell growth and apoptosis. Our data also indicated that the increased apoptotic cell rate may be caused by changes in apoptosis-related genes, such asTNF,TRAILandGnRHR.ConclusionThis study presents a new upstream regulator of FOXL2 and demonstrats that this new STAT3-FOXL2 pathway has an important function in HeLaHeLa cell apoptosis, providing new insights regarding the targeting of FOXL2 for cancer prevention and treatment.