Laboratory of Pharmacoimmunology, Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Seoul, 03722, Republic of Korea.
Institute of Women's Life Medical Science, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Int J Biol Sci. 2020 Jan 1;16(1):99-115. doi: 10.7150/ijbs.35643. eCollection 2020.
Steroid receptor activator (), a long non-coding RNA, serves as a critical regulator of gynecologic cancer. The objective of this study was to determine biological function and clinical significance of expression in endometrial cancer. We investigated whether was involved in the development of endometrial cancer via binding to eukaryotic translation initiation factor 4E-binding protein 1 (EIF4E-BP1) as a transcription factor to enhance Wnt/ β-catenin signaling pathway. Expression levels of were upregulated in endometrial cancer tissues compared to those in adjacent control tissues. We also found high expression of in EC cells. The relationship between and EIF4E-BP1 was corroborated by transfection of a luciferase reporter plasmid. In addition, knockdown inhibited the expression of EIF4E-BP1 known to play a critical role in the control of protein synthesis, cell growth, and cell survival, thus promoting tumourigenesis and epithelial-mesenchymal transition (EMT) important for cell motility and metastasis. Consistently, immunostaining and western blotting analysis showed that expression levels of β-catenin and 4EBP1 in the nucleus were significantly decreased by knockdown but increased by over-expression. These results suggest that is involved in proliferation, migration, and invasion of endometrial cancer cells by increasing the expression of EIF4E-BP1 and activity of Wnt/ β-catenin signaling. These findings indicate that might be a novel biomarker for predicting recurrence and prognosis. It might also serve as a promising therapeutic target in endometrial cancer.
类固醇受体激活物 ()，一种长链非编码 RNA，是妇科癌症的关键调节因子。本研究旨在确定在子宫内膜癌中表达的生物学功能和临床意义。我们通过与真核翻译起始因子 4E 结合蛋白 1 (EIF4E-BP1) 结合作为转录因子来研究是否参与了子宫内膜癌的发生，从而增强 Wnt/β-连环蛋白信号通路。与相邻对照组织相比，子宫内膜癌组织中表达上调。我们还发现 EC 细胞中表达水平较高。转染荧光素酶报告质粒证实了与 EIF4E-BP1 的关系。此外，下调抑制了 EIF4E-BP1 的表达，EIF4E-BP1 在控制蛋白质合成、细胞生长和细胞存活方面发挥着关键作用，从而促进肿瘤发生和上皮-间充质转化 (EMT)，这对于细胞迁移和转移的运动性很重要。一致地，免疫染色和 Western blot 分析表明，下调导致核内β-连环蛋白和 4EBP1 的表达水平显著降低，但过表达则增加。这些结果表明，通过增加 EIF4E-BP1 的表达和 Wnt/β-连环蛋白信号的活性，参与了子宫内膜癌细胞的增殖、迁移和侵袭。这些发现表明可能是预测复发和预后的新型生物标志物。它也可能成为子宫内膜癌有前途的治疗靶点。
