• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

环状FOXO3的上调通过影响细胞代谢组介导胶质母细胞瘤的放射抗性。

CircFOXO3 upregulation mediates the radioresistance of glioblastoma by affecting cellular metabolome.

作者信息

Xu Hao, Xing Jin, Cheng Lilin, Wang Zhihan, Zhao Liang, Ren Li, Zhang Shuai

机构信息

Department of Neurosurgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.

Department of Neurosurgery, Changhai Hospital, Naval Medical University, Shanghai, China.

出版信息

Front Pharmacol. 2024 Oct 10;15:1479480. doi: 10.3389/fphar.2024.1479480. eCollection 2024.

DOI:10.3389/fphar.2024.1479480
PMID:39449966
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11499195/
Abstract

INTRODUCTION

Radioresistance remains a significant challenge in the treatment of glioblastoma multiforme (GBM), the most prevalent and lethal brain cancer in adults. Metabolic alterations are known to contribute to radioresistance by activating antioxidant responses and promoting DNA repair. However, the role of circular RNAs in this process, particularly circFOXO3, is not well understood.

METHODS

In this study, we investigated the expression of circFOXO3 in glioma cells exposed to radiation and in recurrent GBM tissues. We performed knockdown and overexpression experiments and to assess the effects of circFOXO3 on radiosensitivity. Metabolomic profiling was conducted to explore the metabolic changes associated with circFOXO3 overexpression following irradiation.

RESULTS

Our results showed significant upregulation of circFOXO3 in glioma cells upon radiation exposure and in recurrent GBM tissues. Knockdown of circFOXO3 increased radiosensitivity both in vitro and in vivo, whereas overexpression of circFOXO3 attenuated radiosensitivity. Metabolomic analysis revealed substantial alterations in lipid and organic compound profiles between circFOXO3-overexpressing and control groups. Additionally, circFOXO3 suppression increased proapoptotic protein levels (Caspase 7 and Bax) and decreased anti-apoptotic protein Bcl-2 levels following radiotherapy.

DISCUSSION

These findings demonstrate the pivotal role of circFOXO3 in promoting tumor radioresistance through metabolic modulation, suggesting that circFOXO3 could serve as a potential diagnostic and therapeutic target for GBM.

摘要

引言

在多形性胶质母细胞瘤（GBM）的治疗中，放射抗性仍然是一个重大挑战，GBM是成人中最常见且致命的脑癌。已知代谢改变通过激活抗氧化反应和促进DNA修复来促成放射抗性。然而，环状RNA在这一过程中的作用，尤其是circFOXO3的作用，尚未得到充分了解。

方法

在本研究中，我们调查了circFOXO3在接受辐射的胶质瘤细胞和复发性GBM组织中的表达情况。我们进行了敲低和过表达实验，以评估circFOXO3对放射敏感性的影响。进行代谢组学分析，以探索照射后与circFOXO3过表达相关的代谢变化。

结果

我们的结果显示，在辐射暴露后的胶质瘤细胞以及复发性GBM组织中，circFOXO3显著上调。敲低circFOXO3在体外和体内均增加了放射敏感性，而过表达circFOXO3则减弱了放射敏感性。代谢组学分析显示，circFOXO3过表达组与对照组之间的脂质和有机化合物谱有显著变化。此外，放疗后，circFOXO3抑制增加了促凋亡蛋白水平（半胱天冬酶7和Bax），并降低了抗凋亡蛋白Bcl-2水平。

讨论

这些发现证明了circFOXO3在通过代谢调节促进肿瘤放射抗性方面的关键作用，表明circFOXO3可作为GBM的潜在诊断和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/4f0d9b7d13ee/fphar-15-1479480-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/4c7ba144eb89/fphar-15-1479480-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/bbf38d3a3aca/fphar-15-1479480-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/b3d7751c4662/fphar-15-1479480-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/3bb5f49bff4c/fphar-15-1479480-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/0b680fc9e3c0/fphar-15-1479480-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/43959aca18fc/fphar-15-1479480-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/c18d8209f514/fphar-15-1479480-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/4f0d9b7d13ee/fphar-15-1479480-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/4c7ba144eb89/fphar-15-1479480-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/bbf38d3a3aca/fphar-15-1479480-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/b3d7751c4662/fphar-15-1479480-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/3bb5f49bff4c/fphar-15-1479480-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/0b680fc9e3c0/fphar-15-1479480-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/43959aca18fc/fphar-15-1479480-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/c18d8209f514/fphar-15-1479480-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5868/11499195/4f0d9b7d13ee/fphar-15-1479480-g008.jpg

相似文献

1
CircFOXO3 upregulation mediates the radioresistance of glioblastoma by affecting cellular metabolome.环状FOXO3的上调通过影响细胞代谢组介导胶质母细胞瘤的放射抗性。
Front Pharmacol. 2024 Oct 10;15:1479480. doi: 10.3389/fphar.2024.1479480. eCollection 2024.
2
CircFOXO3 promotes glioblastoma progression by acting as a competing endogenous RNA for NFAT5.环状 RNA FOXO3 通过作为 NFAT5 的竞争性内源 RNA 促进神经胶质瘤进展。
Neuro Oncol. 2019 Oct 9;21(10):1284-1296. doi: 10.1093/neuonc/noz128.
3
Cytochrome c oxidase mediates labile iron level and radioresistance in glioblastoma.细胞色素c氧化酶介导胶质母细胞瘤中的不稳定铁水平和放射抗性。
Free Radic Biol Med. 2022 May 20;185:25-35. doi: 10.1016/j.freeradbiomed.2022.04.012. Epub 2022 Apr 25.
4
Knockdown of ATRX enhances radiosensitivity in glioblastoma.敲低ATRX可增强胶质母细胞瘤的放射敏感性。
Chin Neurosurg J. 2024 Jun 19;10(1):19. doi: 10.1186/s41016-024-00371-6.
5
Upregulation of miR-96 promotes radioresistance in glioblastoma cells via targeting PDCD4.miR-96 的上调通过靶向 PDCD4 促进脑胶质瘤细胞的放射抵抗。
Int J Oncol. 2018 Oct;53(4):1591-1600. doi: 10.3892/ijo.2018.4498. Epub 2018 Jul 23.
6
Circular RNA circFOXO3 facilitate non-small cell lung cancer progression through upregulating HMGB3 via sponging miR-545-3p/miR-506-3p.环状 RNA circFOXO3 通过海绵吸附 miR-545-3p/miR-506-3p 而上调 HMGB3 促进非小细胞肺癌进展。
Tissue Cell. 2022 Apr;75:101702. doi: 10.1016/j.tice.2021.101702. Epub 2021 Nov 25.
7
circFOXO3 protects cardiomyocytes against radiation‑induced cardiotoxicity.circFOXO3 可保护心肌细胞免受辐射诱导的心脏毒性。
Mol Med Rep. 2021 Mar;23(3). doi: 10.3892/mmr.2020.11816. Epub 2021 Jan 5.
8
Rab27b contributes to radioresistance and exerts a paracrine effect via epiregulin in glioblastoma.Rab27b促进胶质母细胞瘤的放射抗性，并通过表皮调节素发挥旁分泌作用。
Neurooncol Adv. 2020 Aug 8;2(1):vdaa091. doi: 10.1093/noajnl/vdaa091. eCollection 2020 Jan-Dec.
9
MSI1 associates glioblastoma radioresistance via homologous recombination repair, tumor invasion and cancer stem-like cell properties.MSI1 通过同源重组修复、肿瘤侵袭和癌症干细胞样细胞特性与胶质母细胞瘤的放射抵抗相关。
Radiother Oncol. 2018 Nov;129(2):352-363. doi: 10.1016/j.radonc.2018.09.014. Epub 2018 Oct 12.
10
Smoothened Promotes Glioblastoma Radiation Resistance Via Activating USP3-Mediated Claspin Deubiquitination. smoothened 通过激活 USP3 介导的 claspin 去泛素化促进胶质母细胞瘤的辐射抗性。
Clin Cancer Res. 2020 Apr 1;26(7):1749-1762. doi: 10.1158/1078-0432.CCR-19-1515. Epub 2020 Jan 3.

本文引用的文献

1
Radiotherapy remodels the tumor microenvironment for enhancing immunotherapeutic sensitivity.放疗重塑肿瘤微环境以增强免疫治疗敏感性。
Cell Death Dis. 2023 Oct 13;14(10):679. doi: 10.1038/s41419-023-06211-2.
2
Primary brain tumours in adults.成人原发性脑肿瘤。
Lancet. 2023 Oct 28;402(10412):1564-1579. doi: 10.1016/S0140-6736(23)01054-1. Epub 2023 Sep 19.
3
The Warburg effect on radioresistance: Survival beyond growth.瓦伯格效应与放射抗性：超越生长的存活能力
Biochim Biophys Acta Rev Cancer. 2023 Nov;1878(6):188988. doi: 10.1016/j.bbcan.2023.188988. Epub 2023 Sep 17.
4
FOXO transcription factors as mediators of stress adaptation.FOXO 转录因子作为应激适应的介质。
Nat Rev Mol Cell Biol. 2024 Jan;25(1):46-64. doi: 10.1038/s41580-023-00649-0. Epub 2023 Sep 14.
5
A Cancer Cell Selective Replication Stress Nano Amplifier Promotes Replication Fork Catastrophe to Overcome Radioresistance.一种癌细胞选择性复制应激纳米放大器促进复制叉崩溃以克服放射抵抗性。
ACS Nano. 2023 Sep 26;17(18):18548-18561. doi: 10.1021/acsnano.3c06774. Epub 2023 Sep 14.
6
MMD collaborates with ACSL4 and MBOAT7 to promote polyunsaturated phosphatidylinositol remodeling and susceptibility to ferroptosis.MMD 与 ACSL4 和 MBOAT7 合作，促进多不饱和磷脂酰肌醇重塑和对铁死亡的易感性。
Cell Rep. 2023 Sep 26;42(9):113023. doi: 10.1016/j.celrep.2023.113023. Epub 2023 Sep 8.
7
Mechanisms and applications of radiation-induced oxidative stress in regulating cancer immunotherapy.辐射诱导氧化应激在调控癌症免疫治疗中的机制与应用。
Front Immunol. 2023 Aug 4;14:1247268. doi: 10.3389/fimmu.2023.1247268. eCollection 2023.
8
M2 isoform of pyruvate kinase rewires glucose metabolism during radiation therapy to promote an antioxidant response and glioblastoma radioresistance.丙酮酸激酶 M2 同工型在放射治疗期间重新布线葡萄糖代谢以促进抗氧化反应和胶质母细胞瘤放射抗性。
Neuro Oncol. 2023 Nov 2;25(11):1989-2000. doi: 10.1093/neuonc/noad103.
9
Isoaaptamine increases ROS levels causing autophagy and mitochondria-mediated apoptosis in glioblastoma multiforme cells.异燕麦胺增加活性氧水平，导致多形性胶质母细胞瘤细胞发生自噬和线粒体介导的细胞凋亡。
Biomed Pharmacother. 2023 Apr;160:114359. doi: 10.1016/j.biopha.2023.114359. Epub 2023 Feb 6.
10
Metabolic function of autophagy is essential for cell survival.自噬的代谢功能对于细胞存活是必不可少的。
Autophagy. 2023 Aug;19(8):2395-2397. doi: 10.1080/15548627.2023.2165753. Epub 2023 Feb 1.