• 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

外泌体 circSPIRE1 介导 E-钙黏蛋白糖基化以抑制肾细胞癌转移。

Exosomal circSPIRE1 mediates glycosylation of E-cadherin to suppress metastasis of renal cell carcinoma.

机构信息

Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Department of Food Science and Engineering, Jinan University, Guangzhou, China.

出版信息

Oncogene. 2023 Jun;42(22):1802-1820. doi: 10.1038/s41388-023-02678-7. Epub 2023 Apr 12.

DOI:10.1038/s41388-023-02678-7
PMID:37046045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10238271/
Abstract

Metastasis is the main cause of mortality in renal cell carcinoma (RCC). Circular RNAs (circRNAs) involvement in RCC metastasis has been described, although the underlying mechanisms remain unknown. We evaluated recurring lung-metastasis cases using patient-derived xenograft models and isolated a highly metastatic clone. CircSPIRE1 was identified as a metastasis-inhibiting circRNA in clinical cohort and xenograft models. Mechanistically, circSPIRE1 suppressed mesenchymal state through regulating ELAV like RNA binding protein 1-mRNA binding, and upregulating polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) and KH domain RNA binding protein (QKI) expression. GALNT3 promoted glycosylation and cytomembrane localization of E-cadherin. QKI formed a positive feedback loop to enhance circSPIRE1 expression. Meanwhile, exosomal circSPIRE1 suppressed angiogenesis and vessel permeability. Our work reveals a non-canonical route for circRNAs in RCC to suppress metastasis. Furthermore, a nanomedicine consisting of circSPIRE1 plasmid suppressed metastasis formation. In conclusion, circSPIRE1 may be a predictor of metastasis and a potential therapeutic target of metastatic RCC.

摘要

转移是肾细胞癌（RCC）患者死亡的主要原因。环状 RNA（circRNA）参与 RCC 转移的作用已被描述，但其潜在机制尚不清楚。我们使用患者来源的异种移植模型评估了复发性肺转移病例，并分离出一个高转移性克隆。circSPIRE1 在临床队列和异种移植模型中被鉴定为一种抑制转移的 circRNA。在机制上，circSPIRE1 通过调节 ELAV 样 RNA 结合蛋白 1-mRNA 结合，上调多肽 N-乙酰半乳糖胺转移酶 3（GALNT3）和 KH 结构域 RNA 结合蛋白（QKI）的表达来抑制间充质状态。GALNT3 促进 E-钙黏蛋白的糖基化和细胞表面定位。QKI 形成正反馈环以增强 circSPIRE1 的表达。同时，外泌体 circSPIRE1 抑制血管生成和血管通透性。我们的工作揭示了环状 RNA 在 RCC 中抑制转移的一种非经典途径。此外，由 circSPIRE1 质粒组成的纳米药物抑制了转移的形成。总之，circSPIRE1 可能是转移的预测因子和转移性 RCC 的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/604a1c89d7a8/41388_2023_2678_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/c0deb3122b8c/41388_2023_2678_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/5d824eaeba8e/41388_2023_2678_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/867f6325985c/41388_2023_2678_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/d6dfa9b0054e/41388_2023_2678_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/cde219d7bf70/41388_2023_2678_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/b7bd80e4de75/41388_2023_2678_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/fb964119fb50/41388_2023_2678_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/604a1c89d7a8/41388_2023_2678_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/c0deb3122b8c/41388_2023_2678_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/5d824eaeba8e/41388_2023_2678_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/867f6325985c/41388_2023_2678_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/d6dfa9b0054e/41388_2023_2678_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/cde219d7bf70/41388_2023_2678_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/b7bd80e4de75/41388_2023_2678_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/fb964119fb50/41388_2023_2678_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af02/10238271/604a1c89d7a8/41388_2023_2678_Fig8_HTML.jpg

相似文献

1
Exosomal circSPIRE1 mediates glycosylation of E-cadherin to suppress metastasis of renal cell carcinoma.外泌体 circSPIRE1 介导 E-钙黏蛋白糖基化以抑制肾细胞癌转移。
Oncogene. 2023 Jun;42(22):1802-1820. doi: 10.1038/s41388-023-02678-7. Epub 2023 Apr 12.
2
Down-Regulation of Circular RNA_000926 Attenuates Renal Cell Carcinoma Progression through miRNA-411-Dependent CDH2 Inhibition.环状 RNA_000926 的下调通过 miRNA-411 依赖性 CDH2 抑制来减弱肾细胞癌的进展。
Am J Pathol. 2019 Dec;189(12):2469-2486. doi: 10.1016/j.ajpath.2019.06.016. Epub 2019 Aug 30.
3
circPTCH1 promotes invasion and metastasis in renal cell carcinoma via regulating miR-485-5p/MMP14 axis.环状 RNA PTCH1 通过调控 miR-485-5p/MMP14 轴促进肾细胞癌的侵袭和转移。
Theranostics. 2020 Aug 29;10(23):10791-10807. doi: 10.7150/thno.47239. eCollection 2020.
4
CircTLK1 promotes the proliferation and metastasis of renal cell carcinoma by sponging miR-136-5p.环状 RNA 张力蛋白激酶 1 通过海绵吸附 miR-136-5p 促进肾细胞癌的增殖和转移。
Mol Cancer. 2020 Jun 5;19(1):103. doi: 10.1186/s12943-020-01225-2.
5
Circ-AKT3 inhibits clear cell renal cell carcinoma metastasis via altering miR-296-3p/E-cadherin signals.环状 RNA-AKT3 通过改变 miR-296-3p/E-钙黏蛋白信号抑制透明细胞肾细胞癌转移。
Mol Cancer. 2019 Nov 1;18(1):151. doi: 10.1186/s12943-019-1072-5.
6
CircRNA cRAPGEF5 inhibits the growth and metastasis of renal cell carcinoma via the miR-27a-3p/TXNIP pathway.环状 RNA cRAPGEF5 通过 miR-27a-3p/TXNIP 通路抑制肾细胞癌的生长和转移。
Cancer Lett. 2020 Jan 28;469:68-77. doi: 10.1016/j.canlet.2019.10.017. Epub 2019 Oct 17.
7
The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p.环状 RNA circPTPRA 通过海绵吸附 miR-96-5p 抑制非小细胞肺癌细胞的上皮-间充质转化和转移。
EBioMedicine. 2019 Jun;44:182-193. doi: 10.1016/j.ebiom.2019.05.032. Epub 2019 May 31.
8
circPRRC2A promotes angiogenesis and metastasis through epithelial-mesenchymal transition and upregulates TRPM3 in renal cell carcinoma.环状 RNA PRRC2A 通过上皮-间充质转化促进血管生成和转移，并上调肾细胞癌中的 TRPM3。
Theranostics. 2020 Mar 15;10(10):4395-4409. doi: 10.7150/thno.43239. eCollection 2020.
9
Circ_0000274 contributes to renal cell carcinoma progression by regulating miR-338-3p/NUCB2 axis and JAK1/STAT3 pathway.Circ_0000274 通过调控 miR-338-3p/NUCB2 轴和 JAK1/STAT3 通路促进肾细胞癌进展。
Transpl Immunol. 2022 Oct;74:101626. doi: 10.1016/j.trim.2022.101626. Epub 2022 May 13.
10
microRNA-200c modulates the epithelial-to-mesenchymal transition in human renal cell carcinoma metastasis.miRNA-200c 调控人肾透明细胞癌转移中的上皮间质转化。
Oncol Rep. 2013 Aug;30(2):643-50. doi: 10.3892/or.2013.2530. Epub 2013 Jun 7.

引用本文的文献

1
Natural Antioxidants as Regulators of Circular RNA Expression and Function.天然抗氧化剂作为环状RNA表达和功能的调节剂
Wiley Interdiscip Rev RNA. 2025 Jul-Aug;16(4):e70023. doi: 10.1002/wrna.70023.
2
ELAV mediates circular RNA biogenesis in neurons.ELAV在神经元中介导环状RNA的生物合成。
Genes Dev. 2025 Sep 2;39(17-18):1064-1080. doi: 10.1101/gad.352670.125.
3
Exploring molecular and cellular mechanisms of Pre-Metastatic niche in renal cell carcinoma.探索肾细胞癌中前转移微环境的分子和细胞机制。

本文引用的文献

1
Functions of circular RNAs in bladder, prostate and renal cell cancer (Review).环状 RNA 在膀胱癌、前列腺癌和肾细胞癌中的功能（综述）。
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.11946. Epub 2021 Mar 2.
2
Cancer Statistics, 2021.癌症统计数据，2021.
CA Cancer J Clin. 2021 Jan;71(1):7-33. doi: 10.3322/caac.21654. Epub 2021 Jan 12.
3
CircRNA-SORE mediates sorafenib resistance in hepatocellular carcinoma by stabilizing YBX1.环状 RNA-SORE 通过稳定 YBX1 介导肝癌对索拉非尼的耐药性。
Mol Cancer. 2025 Apr 22;24(1):121. doi: 10.1186/s12943-025-02315-9.
4
RNA sculpting by the primordial Helix-clasp-Helix-Strand-Loop (HcH-SL) motif enforces chemical recognition enabling diverse KH domain functions.由原始螺旋-扣-螺旋-链-环（HcH-SL）基序进行的RNA塑造强化了化学识别，从而实现了多种KH结构域功能。
J Biol Chem. 2025 May;301(5):108474. doi: 10.1016/j.jbc.2025.108474. Epub 2025 Apr 2.
5
Exosomes and solid cancer therapy: where are we now?外泌体与实体癌治疗：我们目前进展如何？
Med Oncol. 2025 Feb 17;42(3):77. doi: 10.1007/s12032-025-02626-3.
6
CircUCK2(2,3) promotes cancer progression and enhances synergistic cytotoxicity of lenvatinib with EGFR inhibitors via activating CNIH4-TGFα-EGFR signaling.环状 UCK2(2,3) 通过激活 CNIH4-TGFα-EGFR 信号通路促进癌症进展并增强乐伐替尼与 EGFR 抑制剂的协同细胞毒性。
Cell Mol Biol Lett. 2025 Jan 30;30(1):15. doi: 10.1186/s11658-025-00690-1.
7
Mechanisms and therapeutic implications of gene expression regulation by circRNA-protein interactions in cancer.环状RNA-蛋白质相互作用在癌症中调控基因表达的机制及治疗意义
Commun Biol. 2025 Jan 17;8(1):77. doi: 10.1038/s42003-024-07383-z.
8
Emerging role of exosomes in cancer therapy: progress and challenges.外泌体在癌症治疗中的新兴作用：进展与挑战
Mol Cancer. 2025 Jan 13;24(1):13. doi: 10.1186/s12943-024-02215-4.
9
RNA-binding protein quaking: a multifunctional regulator in tumour progression.RNA结合蛋白震颤蛋白：肿瘤进展中的多功能调节因子
Ann Med. 2025 Dec;57(1):2443046. doi: 10.1080/07853890.2024.2443046. Epub 2024 Dec 23.
10
Towards Understanding the Role of the Glycosylation of Proteins Present in Extracellular Vesicles in Urinary Tract Diseases: Contributions to Cancer and Beyond.探讨细胞外囊泡中蛋白质糖基化在尿路疾病中的作用：癌症及其他相关疾病的贡献。
Molecules. 2024 Nov 6;29(22):5241. doi: 10.3390/molecules29225241.
Signal Transduct Target Ther. 2020 Dec 26;5(1):298. doi: 10.1038/s41392-020-00375-5.
4
TransCirc: an interactive database for translatable circular RNAs based on multi-omics evidence.TransCirc：基于多组学证据的可翻译环状 RNA 交互式数据库。
Nucleic Acids Res. 2021 Jan 8;49(D1):D236-D242. doi: 10.1093/nar/gkaa823.
5
Circular RNAs in renal cell carcinoma: implications for tumorigenesis, diagnosis, and therapy.环状 RNA 在肾细胞癌中的作用：对肿瘤发生、诊断和治疗的影响。
Mol Cancer. 2020 Oct 14;19(1):149. doi: 10.1186/s12943-020-01266-7.
6
N-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis.N6-甲基腺苷修饰 circNSUN2 促进细胞质输出并稳定 HMGA2 以促进结直肠肝转移。
Nat Commun. 2019 Oct 16;10(1):4695. doi: 10.1038/s41467-019-12651-2.
7
Stage-specific conditional survival in renal cell carcinoma after nephrectomy.肾细胞癌肾切除术后特定阶段的条件生存。
Urol Oncol. 2020 Jan;38(1):6.e1-6.e7. doi: 10.1016/j.urolonc.2019.08.011. Epub 2019 Sep 12.
8
The biogenesis, biology and characterization of circular RNAs.环状 RNA 的生物发生、生物学和特征。
Nat Rev Genet. 2019 Nov;20(11):675-691. doi: 10.1038/s41576-019-0158-7. Epub 2019 Aug 8.
9
5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs.5-甲基胞嘧啶通过稳定 mRNA 促进膀胱癌的发病机制。
Nat Cell Biol. 2019 Aug;21(8):978-990. doi: 10.1038/s41556-019-0361-y. Epub 2019 Jul 29.
10
Functional roles of fucosylated and O-glycosylated cadherins during carcinogenesis and metastasis.糖基化钙黏蛋白在肿瘤发生和转移过程中的功能作用。
Cell Signal. 2019 Nov;63:109365. doi: 10.1016/j.cellsig.2019.109365. Epub 2019 Jul 25.