Overexpression of LSR suppresses glioma proliferation and invasion via regulating FOXO3a.

IF 3.1 2区 医学 Q2 CLINICAL NEUROLOGY Journal of Neuro-Oncology Pub Date : 2025-05-01 Epub Date: 2025-02-24 DOI:10.1007/s11060-025-04976-4
Jinlong Zhu, Tong Wang, Xi Liu, Ting Lu, Jianwei Zhuo, Xiangying Li, Zhengquan Yu, Gang Cui, Haitao Shen
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Abstract

Purpose: Gliomas, the most prevalent type of central nervous system tumors, currently lack effective therapeutic options. Lipolysis-stimulated lipoprotein receptors (LSR) have been implicated in tumor development and progression. This study aims to investigate the influence of LSR on gliomas and elucidate the underlying mechanisms.

Methods: We analyze LSR expression in gliomas and its association with patient prognosis using bioinformatics tools. Western blotting and immunohistochemistry revealed differential expression of LSR across different grades of glioma. The effects of LSR on glioma cell proliferation and invasion are evaluated through a series of cellular assays. Subcutaneous xenografts in nude mice are utilized to assess the impact of LSR on gliomas in vivo. Additionally, western blotting is employed to detect changes in protein levels related to the FOXO3a signaling pathway following LSR overexpression.

Results: LSR expression is higher in tissues from low-grade gliomas compared to those from glioblastomas. Patients with low LSR expression exhibit poorer prognoses. Overexpression of LSR inhibit glioma cell proliferation and invasion. The protein levels of PCNA, Cyclin D1, MMP2, and MMP9 are significantly decreased in the OE-LSR group. Tumor volume is reduced in nude mice injected subcutaneously with LSR-overexpressing glioma cells. Overexpression of LSR increases nuclear FOXO3a level while reduces p-FOXO3a and p-14-3-3 levels. Knockdown of FOXO3a reverse the inhibitory effects of LSR overexpression on glioma cell proliferation and invasion.

Conclusion: Low LSR expression is associated with adverse prognosis in glioma patients. By modulating FOXO3a, LSR overexpression suppresses glioma cell proliferation and invasion.

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过表达LSR通过调控FOXO3a抑制胶质瘤的增殖和侵袭。
目的:神经胶质瘤是最常见的中枢神经系统肿瘤,目前缺乏有效的治疗选择。脂肪酶刺激脂蛋白受体(LSR)参与肿瘤的发生和发展。本研究旨在探讨LSR对胶质瘤的影响并阐明其潜在机制。方法:利用生物信息学工具分析LSR在胶质瘤中的表达及其与患者预后的关系。Western blotting和免疫组化显示LSR在不同级别胶质瘤中的表达差异。通过一系列的细胞实验来评估LSR对胶质瘤细胞增殖和侵袭的影响。利用裸鼠皮下异种移植来评估LSR对体内胶质瘤的影响。此外,western blotting检测LSR过表达后FOXO3a信号通路相关蛋白水平的变化。结果:LSR在低级别胶质瘤组织中的表达高于胶质母细胞瘤组织。低LSR表达的患者预后较差。过表达LSR可抑制胶质瘤细胞的增殖和侵袭。OE-LSR组PCNA、Cyclin D1、MMP2、MMP9蛋白水平明显降低。裸鼠皮下注射过表达lsr的胶质瘤细胞后,肿瘤体积减小。过表达LSR增加细胞核FOXO3a水平,降低p-FOXO3a和p 14-3-3水平。FOXO3a敲低可逆转LSR过表达对胶质瘤细胞增殖和侵袭的抑制作用。结论:低LSR表达与胶质瘤患者的不良预后有关。LSR过表达通过调控FOXO3a抑制胶质瘤细胞的增殖和侵袭。
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来源期刊
Journal of Neuro-Oncology
Journal of Neuro-Oncology 医学-临床神经学
CiteScore
6.60
自引率
7.70%
发文量
277
审稿时长
3.3 months
期刊介绍: The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.
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