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

IF 3.2 2区医学 Q2 CLINICAL NEUROLOGY Journal of Neuro-Oncology Pub 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

{"title":"Overexpression of LSR suppresses glioma proliferation and invasion via regulating FOXO3a.","authors":"Jinlong Zhu, Tong Wang, Xi Liu, Ting Lu, Jianwei Zhuo, Xiangying Li, Zhengquan Yu, Gang Cui, Haitao Shen","doi":"10.1007/s11060-025-04976-4","DOIUrl":null,"url":null,"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.","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neuro-Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11060-025-04976-4","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

求助全文

约1分钟内获得全文去求助

来源期刊

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.