Karkia Rebecca, Sisu Cristina, Saravi Sayeh, Kyrou Ioannis, Randeva Harpal S, Chatterjee Jayanta, Karteris Emmanouil
College of Health, Medicine and Life Sciences, Brunel University of London, Uxbridge UB8 3PH, UK.
Academic Department of Gynaecological Oncology, Royal Surrey NHS Foundation Trust Hospital, Guildford GU2 7XX, UK.
Molecules. 2025 Aug 18;30(16):3410. doi: 10.3390/molecules30163410.
(1) Background: Following the discovery of the adipokine/hormone asprosin, a substantial amount of research has provided evidence for its role in the regulation of glucose homeostasis, as well as appetite, and insulin sensitivity. Its levels are dysregulated in certain disease states, including breast cancer. To date, little is known about its role in endometrial cancer (EC). The present study investigated the effects of asprosin on the transcriptome of the Ishikawa and NOU-1 EC cell lines, and assessed the expression of asprosin's candidate receptors (TLR4, PTPRD, and OR4M1) in health and disease. (2) Methods: tissue culture, RNA extraction, RNA sequencing, reverse transcription-quantitative PCR, gene enrichment and in silico analyses were used for this study. (3) Results: and were significantly downregulated in EC when compared to healthy controls. appeared to have a prognostic role in terms of overall survival (OS) in EC patients (i.e., higher expression, better OS). RNA sequencing revealed that asprosin affected 289 differentially expressed genes (DEGs) in Ishikawa cells and 307 DEGs in NOU-1 cells. Pathway enrichment included apoptosis, glycolysis, hypoxia, and PI3K/AKT/ mTOR/NOTCH signalling for Ishikawa-treated cells. In NOU-1, enriched processes included inflammatory response, epithelial-mesenchymal transition, reactive oxygen species pathways, and interferon gamma responses. Other signalling pathways included mTORC1, DNA repair, and p53, amongst others. (4) Conclusions: These findings underscore the importance of understanding receptor dynamics and signalling pathways in the context of asprosin's role in EC, and provide evidence for a potential role of TLR4 as a diagnostic biomarker.
(1) 背景：在发现脂肪因子/激素阿朴脂蛋白之后，大量研究已为其在调节葡萄糖稳态、食欲及胰岛素敏感性方面的作用提供了证据。其水平在包括乳腺癌在内的某些疾病状态下失调。迄今为止，关于其在子宫内膜癌（EC）中的作用知之甚少。本研究调查了阿朴脂蛋白对石川和NOU - 1子宫内膜癌细胞系转录组的影响，并评估了阿朴脂蛋白候选受体（TLR4、PTPRD和OR4M1）在健康和疾病状态下的表达。(2) 方法：本研究采用组织培养、RNA提取、RNA测序、逆转录定量PCR、基因富集和计算机分析。(3) 结果：与健康对照相比，EC中[此处原文缺失相关基因名称]显著下调。[此处原文缺失相关基因名称]在EC患者的总生存期（OS）方面似乎具有预后作用（即表达越高，OS越好）。RNA测序显示，阿朴脂蛋白影响石川细胞中的289个差异表达基因（DEG）和NOU - 1细胞中的307个DEG。石川处理细胞的通路富集包括凋亡、糖酵解、缺氧和PI3K/AKT/mTOR/NOTCH信号传导。在NOU - 1中，富集过程包括炎症反应、上皮 - 间质转化、活性氧途径和干扰素γ反应。其他信号通路包括mTORC1、DNA修复和p53等。(4) 结论：这些发现强调了在阿朴脂蛋白在EC中的作用背景下理解受体动态和信号通路的重要性，并为TLR4作为诊断生物标志物的潜在作用提供了证据。
