The 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. In 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 as TNF, TRAIL and GnRHR. This 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.

中文翻译：

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新的STAT3-FOXL2通路及其在癌细胞中的功能


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。新兴的研究主要集中在 FOXL2 的下游靶标上，而对其上游调控却知之甚少。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 的调节，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，例如TNF、TRAIL和GnRHR。这项研究提出了一种新的 FOXL2 上游调节因子，并证明了这种新的 STAT3-FOXL2 通路在 HeLaHeLa 细胞凋亡中具有重要功能，为 FOXL2 靶向癌症预防和治疗提供了新的见解。