The YB-1 downstream pathways- diagnostic and therapeutic approaches for endometriosis -

子宫内膜异位症是一种复杂的妇科疾病，被广泛认为是重要的女性健康问题。虽然保守手术如腹腔镜手术和药物治疗仍然是治疗子宫内膜异位症的最佳方法，但它们不能治愈，也不能预防疾病的复发以及长期随访时相关的疼痛症状。增加对子宫内膜异位症分子方面的了解将有助于寻找新的治疗策略。特别是，YB-1在许多类型的人类肿瘤中被认为是特别感兴趣的，因为它在参与细胞稳态的多种分子的转录和翻译调节中起关键作用，以及它与治疗抵抗和复发的显著关联。本课题组前期研究揭示了YB-1参与子宫内膜异位症的发病机制及其在子宫内膜异位症细胞体外扩增和存活中的关键作用。基于这些知识，我们认为YB-1在子宫内膜异位症中值得特别关注，我们的目标是探索YB-1下游通路与子宫内膜异位症细胞存活、进展和侵袭的机制。此外，我们将在小鼠模型中测试磷酸肌醇依赖性激酶-1抑制剂2-氨基- n -[4-[5-（2-菲壬基）-3-（三氟甲基）- h -吡唑-1-基]苯基]-乙酰胺（ou -03012）用于子宫内膜异位症治疗的能力，因为它能够间接阻断YB-1的功能，从而阻断癌细胞中YB-1应答基因的功能。本研究为子宫内膜异位症患者提供了一种新的治疗方法。

Endometriosis is a complex gynecological disease widely recognized as an important women s health issue. Although conservative surgery as laparoscopy procedure and medical therapies are still known to be the best available treatment of endometriosis, they are non-curative and cannot prevent the recurrence of disease as well as related painful symptoms at long-term follow-up. An increased understanding of the molecular aspects in endometriosis would be beneficial in searching novel therapeutic strategies. Particularly, YB-1 has been considered of particular interest in many types of human tumors due to its pivotal role in transcriptional and translational regulation of multiple molecules involved in cellular homeostasis, as well as its significant association with therapy resistance and recurrence. A previous study of our group has revealed the involvement of YB-1 in endometriosis pathogenesis and its critical role in endometriotic cell expansion and survival in vitro. From this knowledge, we believe that YB-1 deserves a special attention in endometriosis and we aim to explore the YB-1 downstream pathways with respect to mechanisms of endometriotic cell survival, progression and invasion. In addition, we are prompting to test the phosphoinositide-dependent kinase-1 inhibitor 2-amino-N-[4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]-acetamide (OSU-03012) for endometriosis treatment in a mouse model based on its ability to indirectly block the function of YB-1 and, consequently, YB-1-responsive genes in cancer cells. This study could provide a novel and promising therapeutic approach for endometriosis patients.