Cancer-associated fibroblasts cells (CAFs) confer a rapid growth and metastasis ability of endometrial cancer (EC) via exosomes-mediated cellular communication. Long non-coding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1) drives the malignant phenotypes of EC cells. However, the role of exosomal NEAT1 from CAFs in EC progression remains ambiguous, which needs to be investigated. In our study, NEAT1 and YKL-40 were up-regulated, while miR-26a/b-5p was down-regulated in EC tissues. Moreover, NEAT1 expression was increased in CAF-exosomes compared with that in NF-exosomes. In addition, the exosomal NEAT1 derived from CAFs could transfer to EC cells and promote YKL-40 expression. Further exploration showed that exosomal NEAT1 enhanced YKL-40 expression via regulating miR-26a/b-5p-STAT3 axis in EC cells. More importantly, exosomal NEAT1 accelerated in vivo tumor growth via miR-26a/b-5p-STAT3-YKL-40 axis. Taken together, our study reveals that exosomal NEAT1 from CAFs contributes to EC progression via miR-26a/b-5p-mediated STAT3/YKL-40 pathway, which indicates the therapeutic potential of exosomal NEAT1 for treating EC.

癌症相关成纤维细胞 (CAF) 通过外泌体介导的细胞通讯赋予子宫内膜癌 (EC) 快速生长和转移的能力。长链非编码 RNA 核富集的丰富转录本 1 (lncRNA NEAT1) 驱动 EC 细胞的恶性表型。然而，来自 CAF 的外泌体 NEAT1 在 EC 进展中的作用仍然模棱两可，需要进一步研究。在我们的研究中，NEAT1 和 YKL-40 上调，而 miR-26a/b-5p 在 EC 组织中下调。此外，与 NF-外泌体相比，CAF-外泌体中 NEAT1 的表达增加。此外，来自 CAFs 的外泌体 NEAT1 可以转移到 EC 细胞并促进 YKL-40 的表达。进一步的探索表明，外泌体 NEAT1 通过调节 EC 细胞中的 miR-26a/b-5p-STAT3 轴来增强 YKL-40 的表达。更重要的是，通过 miR-26a/b-5p-STAT3-YKL-40 轴的体内肿瘤生长。总之，我们的研究表明，来自 CAFs 的外泌体 NEAT1 通过 miR-26a/b-5p 介导的 STAT3/YKL-40 通路促进 EC 进展，这表明外泌体 NEAT1 治疗 EC 的潜力。