miR-338-3p 通过靶向 THBS1 抑制 PI3K/Akt 通路抑制胶质瘤进展。

Mir-338-3p targeting THBS1 attenuates glioma progression by inhibiting the PI3K/Akt pathway.

机构信息

Department of Neurosurgery, , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , 430022, Wuhan, China.

出版信息

Biol Direct. 2024 Jan 24;19(1):9. doi: 10.1186/s13062-023-00443-0.

DOI:10.1186/s13062-023-00443-0

PMID:38267974

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10807173/

Abstract

BACKGROUND

Glioma is a brain tumor with high morbidity and mortality rates. Understanding its molecular pathogenesis can provide targets and therapeutic strategies for glioma treatment. miR-338-3p represses tumor growth in several cancers, including glioma. Thus, this study aimed to identify the regulatory effects of miR-338-3p/phosphoinositide 3-kinase (PI3K)/Akt/thrombospondins 1 (THBS1) on glioma progression.

MATERIALS AND METHODS

Quantitative reverse transcription polymerase chain reaction and western blotting were performed to evaluate the levels of miR-338-3p, THBS1, and PI3K/Akt phosphorylation-related proteins. TargetScan software predicted that miR-338-3p targeted THBS1. This was confirmed by performing the dual-luciferase assay. Wound-healing and cell-counting-kit-8 experiments were performed to analyze how THBS1 and miR-338-3p affect the ability of glioma cells to migrate and proliferate. The effect of miR-338-3p on tumorigenicity in mice was also analyzed.

RESULTS

miR-338-3p downregulation was observed in gliomas, whereas THBS1 showed the opposite trend. By suppressing the PI3K/Akt signaling pathway activation, miR-338-3p overregulated the ability of glioma cells to migrate and proliferate in vitro. Additionally, miR-338-3p inhibited the development of glioma tumors in vivo. Moreover, miR-338-3p directly targeted THBS1. THBS1 overexpression promoted glioma cell migration and proliferation by increasing PI3K/Akt phosphorylation. Nonetheless, miR-338-3p overregulation alleviated the effects of THBS1 overexpression.

CONCLUSION

The miR-338-3p/PI3K/Akt/THBS1 regulatory axis can modulate the progression of glioma cell proliferation and migration; thus, it can be considered a therapeutic biomarker.

摘要

背景

脑肿瘤是一种高发病率和死亡率的疾病。了解其分子发病机制可为脑肿瘤的治疗提供靶点和治疗策略。miR-338-3p 抑制包括脑肿瘤在内的几种癌症的肿瘤生长。因此，本研究旨在确定 miR-338-3p/磷酸肌醇 3-激酶（PI3K）/Akt/血小板反应蛋白 1（THBS1）对脑肿瘤进展的调节作用。

材料和方法

采用定量逆转录聚合酶链反应和蛋白质印迹法检测 miR-338-3p、THBS1 和 PI3K/Akt 磷酸化相关蛋白的水平。TargetScan 软件预测 miR-338-3p 靶向 THBS1。通过双荧光素酶报告基因实验进行验证。采用划痕愈合和细胞计数试剂盒-8 实验分析 THBS1 和 miR-338-3p 如何影响脑肿瘤细胞的迁移和增殖能力。还分析了 miR-338-3p 对小鼠肿瘤生成的影响。

结果

在脑肿瘤中观察到 miR-338-3p 的下调，而 THBS1 则呈现相反的趋势。通过抑制 PI3K/Akt 信号通路的激活，miR-338-3p 上调了脑肿瘤细胞在体外的迁移和增殖能力。此外，miR-338-3p 抑制了体内脑肿瘤的发展。此外，miR-338-3p 直接靶向 THBS1。THBS1 过表达通过增加 PI3K/Akt 磷酸化促进脑肿瘤细胞的迁移和增殖。然而，miR-338-3p 的过表达缓解了 THBS1 过表达的作用。