南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (9): 1447-1459.doi: 10.12122/j.issn.1673-4254.2023.09.01

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miRNA-128-3p通过下调KLHDC8A的表达抑制胶质瘤细胞的恶性生物学行为

于正涛，李佳梦，蒋俊文，李 由，林 珑，夏 鹰，王 磊   

  1. 中南大学湘雅医学院附属海口医院神经外科，海南 海口 570208；中南大学湘雅医学院附属肿瘤医院神经外科，湖南 长沙 410006
  • 出版日期:2023-09-20 发布日期:2023-09-28

miRNA-128-3p inhibits malignant behavior of glioma cells by downregulating KLHDC8A expression

YU Zhengtao, LI Jiameng, JIANG Junwen, LI You, LIN Long, XIA Ying, WANG Lei   

  1. Department of Neurosurgery, Affiliated Haikou Hospital of Xiangya School of Central South University, Haikou 570208, China; Department of Neurosurgery, Hunan Cancer Hospital and Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410006, China
  • Online:2023-09-20 Published:2023-09-28

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摘要： 目的 探讨miRNA-128-3p在胶质瘤细胞中的作用，并确定其是否能够调控KLHDC8A介导恶性生物学行为，为寻找胶质瘤患者潜在的分子生物标志物和治疗靶点提供理论支持。方法 采用双荧光素酶报告基因、qRT-PCR和Western blotting实验验证miRNA-128-3p与KLHDC8A的调控关系。通过Edu实验 、流式细胞术、Transwell和划痕实验验证miRNA-128-3p和KLHDC8A对胶质瘤细胞恶性行为的影响。利用挽救实验验证miRNA-128-3p靶向KLHDC8A调控胶质瘤细胞的增殖、凋亡、侵袭和迁移。结果 KLHDC8A在高级别胶质瘤组织中的表达水平显著升高，与恶性胶质瘤患者的生存状况密切相关。功能验证实验表明，高表达KLHDC8A可促进胶质瘤细胞的增殖、迁移和侵袭，而miRNA-128-3p高表达抑制胶质瘤细胞的增殖、迁移等恶性生物学行为。miRNA-128-3p靶向调节胶质瘤细胞中KLHDC8A的表达，miRNA-128-3p高表达通过靶向KLHDC8A抑制胶质瘤细胞的恶性生物学行为。结论 miRNA-128-3p 负向调控其下游靶基因KLHDC8A的表达，抑制胶质瘤细胞恶性生物学行为，因此miRNA-128-3p/KLHDC8A是判断胶质瘤预后及治疗的分子靶点。

关键词: 胶质瘤；miRNA-128-3p；KLHDC8A；生物标志物；迁移；增殖

Abstract: Objective To determine whether miRNA-128-3p regulates malignant biological behavior of glioma cells by targeting KLHDC8A. Methods Dual-luciferase reporter assays, qRT-PCR and Western blotting were used to verify the targeting of miRNA-128-3p to KLHDC8A. Edu assay, flow cytometry, Transwell assay and would healing assay were used to determine the effects of changes in miRNA-128-3p and KLHDC8A expression levels on malignant behavior of glioma cells. Rescue experiment was carried out to verify that miRNA-128-3p regulated glioma cell proliferation, apoptosis, invasion and migration by targeting KLHDC8A. Results The expression level of KLHDC8A was significantly increased in high-grade glioma tissue and was closely related to a poor survival outcome of the patients. Overexpression of KLHDC8A promoted glioma cell proliferation, migration and invasion, and miRNA-128-3p overexpression inhibited proliferative and metastatic capacities of glioma cells. Mechanistically, KLHDC8A expression was directly modulated by miRNA-128-3p, which, by targeting KLHDC8A, inhibited malignant behavior of glioma cells. Conclusion Upregulation of miRNA-128-3p inhibits uncontrolled growth of glioma cells by negatively regulating KLHDC8A expression and its downstream effectors, suggesting that the miRNA-128-3p-KLHDC8A axis may serve as a potential prognostic indicator and a therapeutic target for developing new strategies for glioma treatment.

Key words: glioma; miRNA-128-3p; KLHDC8A; biomarker; migration; proliferation