基础医学与临床 ›› 2025, Vol. 45 ›› Issue (12): 1580-1587.doi: 10.16352/j.issn.1001-6325.2025.12.1580

• 研究论文 • 上一篇    下一篇

miR-141-3p下调溶血磷脂酸受体3抑制脑胶质瘤细胞增殖、迁移和上皮-间质转化

李文辉1, 任红岗1, 郭剑1, 宋洋1, 冯富强2*   

  1. 1.临汾市人民医院 神经外科,山西 临汾 041000;
    2.山西省肿瘤医院 中国医学科学院肿瘤医院山西医院 山西医科大学附属肿瘤医院 神经外科,山西 太原 030013
  • 收稿日期:2025-01-16 修回日期:2025-03-25 出版日期:2025-12-05 发布日期:2025-11-25
  • 通讯作者: *doctorfengfuqiang@163.com
  • 基金资助:
    山西省基础研究计划(20210302123265);山西省卫生健康委科研课题(2021060)

miR-141-3p down-regulating lysophosphatidic acid receptor3 inhibits proliferation, migration and epithelial-mesenchymal transition of brain glioma cells

LI Wenhui1, REN Honggang1, GUO Jian1, SONG Yang1, FENG Fuqiang2*   

  1. 1. Department of Neurosurgery, Linfen People′s Hospital, Linfen 041000;
    2. Department of Neurosurgery, Shanxi Cancer Hospital, Chinese Academy of Medical Sciences Cancer Hospital Shanxi Hospital, the Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan 030013, China
  • Received:2025-01-16 Revised:2025-03-25 Online:2025-12-05 Published:2025-11-25
  • Contact: *doctorfengfuqiang@163.com

摘要: 目的 探讨miR-141-3p调控溶血磷脂酸受体3(LPAR3)对脑胶质瘤细胞增殖、迁移和上皮细胞-间质转化的影响。方法 RT-qPCR检测脑胶质瘤组织及细胞中miR-141-3p、LPAR3 mRNA水平;双荧光素酶检测miR-141-3p与LPAR3的靶向关系;将细胞分为control组、miR-NC组、miR-141-3p mimics组、miR-141-3p mimics+pcDNA3.1组、miR-141-3p mimics+pcDNA-LPAR3组,分别转染相应质粒24 h;RT-qPCR检测细胞中miR-141-3p、LPAR3 mRNA水平;EdU检测细胞增殖;划痕愈合实验检测细胞迁移;Western blot检测细胞增殖、迁移和上皮细胞-间质转化相关蛋白表达;裸鼠移植瘤实验观察瘤形成情况,RT-qPCR检测瘤组织miR-141-3p水平,Western blot检测LPAR3、PCNA、MMP-2表达。结果 在脑胶质瘤组织及U251、T98G、CHG-5细胞中miR-141-3p水平降低,LPAR3 mRNA水平升高(P<0.05);miR-141-3p与LPAR3之间存在靶向结合位点;miR-141-3p mimics可升高miR-141-3p水平及E-cadherin表达,降低LPAR3 mRNA水平、EdU阳性率、划痕愈合率、PCNA、cyclin D1、MMP-2、MMP-9、N-cadherin、vimentin表达(P<0.05);pcDNA-LPAR3可逆转上述因子表达趋势(P<0.05);裸鼠移植瘤实验显示,miR-141-3p mimics可降低瘤体积、瘤重及LPAR3、PCNA、MMP-2表达,升高miR-141-3p水平(P<0.05)。结论 miR-141-3p可通过下调LPAR3抑制脑胶质瘤细胞增殖、迁移、上皮细胞-间质转化。

关键词: miR-141-3p, 溶血磷脂酸受体3, 脑胶质瘤细胞, 增殖, 上皮-间质转化

Abstract: Objective To investigate the impacts of miR-141-3p on the proliferation, migration and epithelial-mesenchymal transformation of glioma cells by regulating lysophosphatidic acid receptor 3 (LPAR3). Methods RT-qPCR was used to detect the level of miR-141-3p and LPAR3 in glioma tissues and cells. Dual luciferase was used to detect the targeting relationship between miR-141-3p and LPAR3. The cells were divided into control group, miR-NC group, miR-141-3p mimics group, miR-141-3p mimics+pcDNA3.1 group, and miR-141-3p mimics+pcDNA-LPAR3 group, and then transfected with corresponding plasmids. RT-qPCR was used to detect the level of miR-141-3p and LPAR3 in cells. EdU method was used to detect cell proliferation. The scratch healing experiment was used to detect cell migration. Western blot was used to detect the expression of proteins related to cell proliferation, migration, and epithelial-mesenchymal transformation. Xenograft tumor model in nude mice was used to observe tumor formation. RT-qPCR was used to detect the level of miR-141-3p in tumor tissue. In addition, Western blot was performed to detect the expression of LPAR3, PCNA, and MMP-2. Results miR-141-3p was downregulated, whereas LPAR3 mRNA was upregulated in glioma tissues and U251, T98G, and CHG-5 cell lines (P<0.05). There was a targeted binding site between miR-141-3p and LPAR3. miR-141-3p mimics significantly increased the expression of miR-141-3p and E-cadherin, but decreased LPAR3 mRNA level, EdU-positive rate, scratch wound healing rate, and the expression of PCNA, cyclin D1, MMP-2, MMP-9, N-cadherin, and vimentin (P<0.05). pcDNA-LPAR3 reversed effect on expression of these factors (P<0.05). Tumor transplantation experiments in nude mice showed that miR-141-3p mimics reduced tumor volume, tumor weight, LPAR3, PCNA, and MMP-2 expression, and increased the level of miR-141-3p (P<0.05). Conclusions miR-141-3p can inhibit proliferation, migration, and epithelial-mesenchymal transformation of glioma cells by down-regulating LPAR3.

Key words: miR-141-3p, lysophosphatidic acid receptor 3, glioma cell, proliferation, epithelial-mesenchymal transformation

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