实用医学杂志 ›› 2022, Vol. 38 ›› Issue (19): 2400-2406.doi: 10.3969/j.issn.1006⁃5725.2022.19.005

• 基础研究 • 上一篇    下一篇

肿瘤来源外泌体miR⁃106a对肝母细胞瘤及其免疫微环境的影响 

任巧利 李艳超    

  1. 广州市妇女儿童医疗中心(广州510006

  • 出版日期:2022-10-10 发布日期:2022-10-10
  • 通讯作者: 李艳超 E⁃mail:1048122620@qq.com
  • 基金资助:
    广东省医学科学技术研究基金项目(编号:B2022233)

Effects of tumor ⁃ derived exosome miR ⁃ 106a on hepatoblastoma and immune microenvironment

REN QiaoliLI Yanchao.   

  1. Guangzhou Women and Children′s Medical CenterGuangzhou 510006China

  • Online:2022-10-10 Published:2022-10-10
  • Contact: LI Yanchao E⁃mail:1048122620@qq.com

摘要:

目的 本研究旨在探讨肝母细胞瘤(HB)来源外泌体 miR⁃106a 对细胞通讯及免疫微环境的 重要作用。方法 超速离心从 HB 细胞中分离外泌体,用透射电子显微镜观察表型。体外实验检测肿瘤 细胞的增殖与迁移能力;双荧光素酶报告基因实验验证 miR⁃106a 和磷酸酶张力蛋白同源物(PTEN)的 3′⁃UTR的靶向关系;动物实验及流式细胞术验证miR⁃106a对于免疫微环境及肿瘤生长的影响。结果 研究发现,HB 细胞释放的外泌体中富含 miR⁃106aP = 0.000 6),该 miRNA 增强了 HB 细胞的增殖(P = 0.0064) 和迁移能力(P = 0.000 3)。此外,外泌体 miR⁃106a 直接与 PTEN 3′⁃UTR 结合,抑制其表达(P = 0.000 5), 激活AKT 信号通路,促进血管生长因子(VEGF)的分泌(P = 0.005 8)。动物实验证实,miR⁃106a 通过VEGF 募集髓源性抑制细胞(MDSCs)进入肿瘤微环境(P = 0.000 8),促进肿瘤生长(P = 0.000 1)。结论 肿瘤来 源外泌体促进HB 细胞的增殖及迁移,并上调VEGF 分泌,募集MDSCs 进入肿瘤微环境,促进肿瘤生长。

关键词:

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肝母细胞瘤, 外泌体, miR?106a, 增殖, 免疫微环境

Abstract: Objective To investigate the role of hepatoblastomaHB⁃derived exosome miR⁃106a in cell communication and immune microenvironment. Methods Exosomes were isolated from HB cells by supercentrifu⁃ gation and phenotypes were observed by transmission electron microscope. The proliferation and migration of tumor cells were detected in vitro. Dual luciferase reporter assay was used to verify the 3′ ⁃UTR targeting relationship between miR⁃106a and phosphatase tension protein homologPTEN. The effects of miR⁃106a on immune microen⁃ vironment and tumor growth were verified by animal experiments and flow cytometry. Results The exosomes released by HB cells were rich in miR⁃106aP = 0.000 6),which enhanced the proliferationP = 0.006 4and migrationP = 0.000 3of HB cells. In additionthe exosome miR⁃106a directly bound to the 3′⁃UTR of PTEN to inhibit its expressionP = 0.000 5),activating the AKT signaling pathway and promoting the secretion of vascular growth factorVEGF)(P = 0.005 8. Animal experiments confirmed that miR⁃106acould recruit myeloid suppressor cellsMDSCsthrough VEGF to enter tumor microenvironmentP = 0.000 8and promote tumor growthP = 0.000 1Conclusion HB⁃derived exosomes promote the proliferation and migration of tumor cells up⁃regulate VEGF secretionrecruit MDSCs into tumor microenvironmentand promote tumor growth.

Key words:

hepatoblastoma, exosome, miR?106a, proliferation, immune?microenvironment