IGF2BP2 inhibits invasion and migration of clear cell renal cell carcinoma via targeting Netrin-4 in an m6A-dependent manner.

IF 3 2区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Carcinogenesis Pub Date : 2024-08-01 Epub Date: 2024-05-23 DOI:10.1002/mc.23746
Gui Wang, Tao Zhuang, Fei Zhen, Chu Zhang, Qichao Wang, Xu Miao, Nienie Qi, Ruiqin Yao
{"title":"IGF2BP2 inhibits invasion and migration of clear cell renal cell carcinoma via targeting Netrin-4 in an m<sup>6</sup>A-dependent manner.","authors":"Gui Wang, Tao Zhuang, Fei Zhen, Chu Zhang, Qichao Wang, Xu Miao, Nienie Qi, Ruiqin Yao","doi":"10.1002/mc.23746","DOIUrl":null,"url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma, often leads to a poor prognosis due to metastasis. The investigation of N6-methyladenosine (m<sup>6</sup>A) methylation, a crucial RNA modification, and its role in ccRCC, particularly through the m<sup>6</sup>A reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), revealed significant insights. We found that IGF2BP2 was notably downregulated in ccRCC, which correlated with tumor aggressiveness and poor prognosis. Thus, IGFBP2 has emerged as an independent prognostic factor of ccRCC. Moreover, a strong positive correlation was observed between the expression of IGF2BP2 and Netrin-4. Netrin-4 was also downregulated in ccRCC, and its lower levels were associated with increased malignancy and poor prognosis. Overexpression of IGF2BP2 and Netrin-4 suppressed the invasion and migration of ccRCC cells, while Netrin-4 knockdown reversed these effects in ccRCC cell lines. RNA immunoprecipitation (RIP)-quantitative polymerase chain reaction validated the robust enrichment of Netrin-4 mRNA in anti-IGF2BP2 antibody immunoprecipitates. MeRlP showed significantly increased Netrin4 m<sup>6</sup>A levels after lGF2BP2 overexpression. Moreover, we found that IGF2BP2 recognized and bound to the m<sup>6</sup>A site within the coding sequence of Netrin-4, enhancing its mRNA stability. Collectively, these results showed that IGF2BP2 plays a suppressive role in the invasion and migration of ccRCC cells by targeting Netrin-4 in an m<sup>6</sup>A-dependent manner. These findings underscore the potential of IGF2BP2/Netrin-4 as a promising prognostic biomarker and therapeutic target in patients with ccRCC metastasis.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1572-1587"},"PeriodicalIF":3.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Carcinogenesis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/mc.23746","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/23 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma, often leads to a poor prognosis due to metastasis. The investigation of N6-methyladenosine (m6A) methylation, a crucial RNA modification, and its role in ccRCC, particularly through the m6A reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), revealed significant insights. We found that IGF2BP2 was notably downregulated in ccRCC, which correlated with tumor aggressiveness and poor prognosis. Thus, IGFBP2 has emerged as an independent prognostic factor of ccRCC. Moreover, a strong positive correlation was observed between the expression of IGF2BP2 and Netrin-4. Netrin-4 was also downregulated in ccRCC, and its lower levels were associated with increased malignancy and poor prognosis. Overexpression of IGF2BP2 and Netrin-4 suppressed the invasion and migration of ccRCC cells, while Netrin-4 knockdown reversed these effects in ccRCC cell lines. RNA immunoprecipitation (RIP)-quantitative polymerase chain reaction validated the robust enrichment of Netrin-4 mRNA in anti-IGF2BP2 antibody immunoprecipitates. MeRlP showed significantly increased Netrin4 m6A levels after lGF2BP2 overexpression. Moreover, we found that IGF2BP2 recognized and bound to the m6A site within the coding sequence of Netrin-4, enhancing its mRNA stability. Collectively, these results showed that IGF2BP2 plays a suppressive role in the invasion and migration of ccRCC cells by targeting Netrin-4 in an m6A-dependent manner. These findings underscore the potential of IGF2BP2/Netrin-4 as a promising prognostic biomarker and therapeutic target in patients with ccRCC metastasis.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
IGF2BP2 以 m6A 依赖性方式通过靶向 Netrin-4 抑制透明细胞肾细胞癌的侵袭和迁移。
透明细胞肾细胞癌(ccRCC)是肾细胞癌中最常见的亚型,往往因转移而导致预后不良。N6-甲基腺苷(m6A)甲基化是一种关键的RNA修饰,研究它在ccRCC中的作用,特别是通过m6A读取胰岛素样生长因子2 mRNA结合蛋白2(IGF2BP2)的甲基化,揭示了重要的见解。我们发现,IGF2BP2 在 ccRCC 中明显下调,这与肿瘤的侵袭性和预后不良有关。因此,IGFBP2 已成为 ccRCC 的一个独立预后因素。此外,还观察到 IGF2BP2 的表达与 Netrin-4 之间存在很强的正相关性。Netrin-4也在ccRCC中下调,其水平较低与恶性程度增加和预后不良有关。在ccRCC细胞系中,过表达IGF2BP2和Netrin-4可抑制ccRCC细胞的侵袭和迁移,而Netrin-4的敲除可逆转这些效应。RNA免疫沉淀(RIP)-定量聚合酶链反应验证了抗IGF2BP2抗体免疫沉淀物中Netrin-4 mRNA的强力富集。MeRlP显示,lGF2BP2过表达后,Netrin4 m6A水平明显增加。此外,我们还发现 IGF2BP2 能识别并结合 Netrin-4 编码序列中的 m6A 位点,从而增强其 mRNA 的稳定性。总之,这些结果表明,IGF2BP2 通过以 m6A 依赖性方式靶向 Netrin-4 在 ccRCC 细胞的侵袭和迁移中起抑制作用。这些发现强调了IGF2BP2/Netrin-4作为ccRCC转移患者预后生物标志物和治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Molecular Carcinogenesis
Molecular Carcinogenesis 医学-生化与分子生物学
CiteScore
7.30
自引率
2.20%
发文量
112
审稿时长
2 months
期刊介绍: Molecular Carcinogenesis publishes articles describing discoveries in basic and clinical science of the mechanisms involved in chemical-, environmental-, physical (e.g., radiation, trauma)-, infection and inflammation-associated cancer development, basic mechanisms of cancer prevention and therapy, the function of oncogenes and tumors suppressors, and the role of biomarkers for cancer risk prediction, molecular diagnosis and prognosis.
期刊最新文献
Inhibition of XPR1-dependent phosphate efflux induces mitochondrial dysfunction: A potential molecular target therapy for hepatocellular carcinoma? Oncogenic fusion of CD63-BCAR4 contributes cancer stem cell-like properties via ALDH1 activity. SIRT1 promotes doxorubicin-induced breast cancer drug resistance and tumor angiogenesis via regulating GSH-mediated redox homeostasis. Oscillatory hypoxia induced gene expression predicts low survival in human breast cancer patients. ROR2 promotes cell cycle progression and cell proliferation through the PI3K/AKT signaling pathway in gastric cancer.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1