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，被广泛认为是女性S的重要健康问题。虽然保守手术如腹腔镜术和内科治疗仍是目前已知的治疗子宫内膜异位症的最佳方法，但它们都是非根治性的，在长期的随访中不能预防疾病的复发和相关的疼痛症状。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。尤其是，YB-1在许多类型的人类肿瘤中被认为是特别感兴趣的，因为它在参与细胞动态平衡的多个分子的转录和翻译调节中起着关键作用，并且它与治疗抵抗和复发密切相关。本课题组先前的一项研究揭示了YB-1参与了子宫内膜异位症的发病机制，以及它在子宫内膜异位症细胞体外扩增和存活中的关键作用。基于这些认识，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下游通路在子宫内膜异位症细胞生存、进展和侵袭机制中的作用。此外，我们还建议在小鼠模型中测试肌醇磷脂依赖的激酶-1抑制剂2-amino-N-[4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]-acetamide(OSU-03012)用于治疗子宫内膜异位症的能力，因为它能够间接阻断YB-1的功能，从而阻断癌细胞中YB-1反应基因。本研究为子宫内膜异位症患者的治疗提供了一种新的、有前景的治疗方法。

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.