Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Province, PR China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Province, PR China.
Neoplasia. 2021 Jul;23(7):692-703. doi: 10.1016/j.neo.2021.05.004. Epub 2021 Jun 18.
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（CAFs）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 核富集丰富转录本 1（lncRNA NEAT1）驱动 EC 细胞的恶性表型。然而，CAFs 来源的外泌体 NEAT1 在 EC 进展中的作用仍不明确，需要进一步研究。在我们的研究中，EC 组织中 NEAT1 和 YKL-40 上调，而 miR-26a/b-5p 下调。此外，与 NF-外泌体相比，CAF-外泌体中的 NEAT1 表达增加。此外，CAFs 来源的外泌体 NEAT1 可转移至 EC 细胞并促进 YKL-40 表达。进一步探索表明，外泌体 NEAT1 通过调节 EC 细胞中的 miR-26a/b-5p-STAT3 轴增强 YKL-40 表达。更重要的是，外泌体 NEAT1 通过 miR-26a/b-5p-STAT3-YKL-40 轴加速体内肿瘤生长。总之，我们的研究表明，CAFs 来源的外泌体 NEAT1 通过 miR-26a/b-5p 介导的 STAT3/YKL-40 通路促进 EC 的进展，这表明外泌体 NEAT1 在治疗 EC 方面具有治疗潜力。
