• 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

长链非编码 RNA CDKN2B-AS1 被 IGF2BP3 稳定，通过表观遗传激活 NUF2 转录驱动肾透明细胞癌的恶性转化。

LncRNA CDKN2B-AS1 stabilized by IGF2BP3 drives the malignancy of renal clear cell carcinoma through epigenetically activating NUF2 transcription.

机构信息

Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, 518000, Shenzhen, Guangdong, China.

Department of Minimally Invasive Intervention, Peking University Shenzhen Hospital, 518000, Shenzhen, Guangdong, China.

出版信息

Cell Death Dis. 2021 Feb 19;12(2):201. doi: 10.1038/s41419-021-03489-y.

DOI:10.1038/s41419-021-03489-y
PMID:33608495
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7895987/
Abstract

Because of the lack of sensitivity to radiotherapy and chemotherapy, therapeutic options for renal clear cell carcinoma (KIRC) are scarce. Long noncoding RNAs (lncRNAs) play crucial roles in the progression of cancer. However, their functional roles and upstream mechanisms in KIRC remain largely unknown. Exploring the functions of potential essential lncRNAs may lead to the discovery of novel targets for the diagnosis and treatment of KIRC. Here, according to the integrated analysis of RNA sequencing and survival data in TCGA-KIRC datasets, cyclin-dependent kinase inhibitor 2B antisense lncRNA (CDKN2B-AS1) was discovered to be the most upregulated among the 14 lncRNAs that were significantly overexpressed in KIRC and related to shorter survival. Functionally, CDKN2B-AS1 depletion suppressed cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, CDKN2B-AS1 exerted its oncogenic activity by recruiting the CREB-binding protein and SET and MYND domain-containing 3 epigenetic-modifying complex to the promoter region of Ndc80 kinetochore complex component (NUF2), where it epigenetically activated NUF2 transcription by augmenting local H3K27ac and H3K4me3 modifications. Moreover, we also showed that CDKN2B-AS1 interacted with and was stabilized by insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an oncofetal protein showing increased levels in KIRC. The Kaplan-Meier method and receiver operating curve analysis revealed that patients whose IGF2BP3, CDKN2B-AS1 and NUF2 are all elevated showed the shortest survival time, and the combined panel (containing IGF2BP3, CDKN2B-AS1, and NUF2) possessed the highest accuracy in discriminating high-risk from low-risk KIRC patients. Thus, we conclude that the stabilization of CDKN2B-AS1 by IGF2BP3 drives the malignancy of KIRC through epigenetically activating NUF2 transcription and that the IGF2BP3/CDKN2B-AS1/NUF2 axis may be an ideal prognostic and diagnostic biomarker and therapeutic target for KIRC.

摘要

由于对放疗和化疗的敏感性不足，肾透明细胞癌（KIRC）的治疗选择有限。长链非编码 RNA（lncRNA）在癌症的进展中起着至关重要的作用。然而，它们在 KIRC 中的功能作用和上游机制在很大程度上仍然未知。探索潜在的必需 lncRNA 的功能可能会发现 KIRC 诊断和治疗的新靶点。在这里，根据 TCGA-KIRC 数据集的 RNA 测序和生存数据的综合分析，发现细胞周期蛋白依赖性激酶抑制剂 2B 反义 lncRNA（CDKN2B-AS1）是在 KIRC 中表达显著上调且与生存时间较短相关的 14 个 lncRNA 中上调最明显的。功能上，CDKN2B-AS1 缺失抑制了体外和体内的细胞增殖、迁移和侵袭。在机制上，CDKN2B-AS1 通过募集 CREB 结合蛋白和 SET 和 MYND 结构域包含 3 个表观遗传修饰复合物到 Ndc80 着丝粒复合物成分（NUF2）的启动子区域，通过增加局部 H3K27ac 和 H3K4me3 修饰来表观激活 NUF2 转录，从而发挥其致癌活性。此外，我们还表明，CDKN2B-AS1 与胰岛素样生长因子 2 mRNA 结合蛋白 3（IGF2BP3）相互作用并稳定 IGF2BP3，IGF2BP3 是一种癌胚蛋白，在 KIRC 中水平升高。Kaplan-Meier 方法和接收者操作曲线分析显示，IGF2BP3、CDKN2B-AS1 和 NUF2 均升高的患者的生存时间最短，而包含 IGF2BP3、CDKN2B-AS1 和 NUF2 的联合组在区分高危和低危 KIRC 患者方面具有最高的准确性。因此，我们得出结论，IGF2BP3 稳定 CDKN2B-AS1 通过表观激活 NUF2 转录驱动 KIRC 的恶性程度，IGF2BP3/CDKN2B-AS1/NUF2 轴可能是 KIRC 的理想预后和诊断生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/7895987/75d495c29269/41419_2021_3489_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/7895987/d822dbf6da06/41419_2021_3489_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/7895987/a871d4b709b0/41419_2021_3489_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/7895987/70c808ea0b22/41419_2021_3489_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/7895987/d9999f673fb1/41419_2021_3489_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/7895987/437e63bb400f/41419_2021_3489_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/7895987/75d495c29269/41419_2021_3489_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/7895987/d822dbf6da06/41419_2021_3489_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/7895987/a871d4b709b0/41419_2021_3489_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/7895987/70c808ea0b22/41419_2021_3489_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/7895987/d9999f673fb1/41419_2021_3489_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/7895987/437e63bb400f/41419_2021_3489_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/7895987/75d495c29269/41419_2021_3489_Fig6_HTML.jpg

相似文献

1
LncRNA CDKN2B-AS1 stabilized by IGF2BP3 drives the malignancy of renal clear cell carcinoma through epigenetically activating NUF2 transcription.长链非编码 RNA CDKN2B-AS1 被 IGF2BP3 稳定，通过表观遗传激活 NUF2 转录驱动肾透明细胞癌的恶性转化。
Cell Death Dis. 2021 Feb 19;12(2):201. doi: 10.1038/s41419-021-03489-y.
2
lncRNA MSC-AS1 activates Wnt/β-catenin signaling pathway to modulate cell proliferation and migration in kidney renal clear cell carcinoma via miR-3924/WNT5A.长链非编码 RNA MSC-AS1 通过 miR-3924/WNT5A 激活 Wnt/β-catenin 信号通路调节肾透明细胞癌细胞增殖和迁移。
J Cell Biochem. 2020 Oct;121(10):4085-4093. doi: 10.1002/jcb.29594. Epub 2020 Jan 9.
3
LncRNA CDKN2B-AS1/miR-141/cyclin D network regulates tumor progression and metastasis of renal cell carcinoma.LncRNA CDKN2B-AS1/miR-141/cyclin D 网络调控肾细胞癌的肿瘤进展和转移。
Cell Death Dis. 2020 Aug 19;11(8):660. doi: 10.1038/s41419-020-02877-0.
4
Downregulation of lncRNA ZNF582-AS1 due to DNA hypermethylation promotes clear cell renal cell carcinoma growth and metastasis by regulating the N(6)-methyladenosine modification of MT-RNR1.由于 DNA 过度甲基化导致长非编码 RNA ZNF582-AS1 下调，通过调节 MT-RNR1 的 N(6)-甲基腺苷修饰促进肾透明细胞癌的生长和转移。
J Exp Clin Cancer Res. 2021 Mar 10;40(1):92. doi: 10.1186/s13046-021-01889-8.
5
LncRNA CDKN2B-AS1 promotes tumor growth and metastasis of human hepatocellular carcinoma by targeting let-7c-5p/NAP1L1 axis.LncRNA CDKN2B-AS1 通过靶向 let-7c-5p/NAP1L1 轴促进人肝癌的肿瘤生长和转移。
Cancer Lett. 2018 Nov 28;437:56-66. doi: 10.1016/j.canlet.2018.08.024. Epub 2018 Aug 27.
6
Upregulated lncRNA Cyclin-dependent kinase inhibitor 2B antisense RNA 1 induces the proliferation and migration of colorectal cancer by miR-378b/CAPRIN2 axis.上调的 lncRNA 细胞周期蛋白依赖性激酶抑制剂 2B 反义 RNA 1 通过 miR-378b/CAPRIN2 轴诱导结直肠癌细胞的增殖和迁移。
Bioengineered. 2021 Dec;12(1):5476-5490. doi: 10.1080/21655979.2021.1961656.
7
-Mediated Regulation of mA-Modified by mA Reader IGF2BP3 Drives ccRCC Progression.-mA 修饰物 IGF2BP3 通过 mA 阅读器介导的调控驱动 ccRCC 进展。
Cancer Res. 2021 Feb 15;81(4):923-934. doi: 10.1158/0008-5472.CAN-20-1619. Epub 2020 Dec 8.
8
LINC00997, a novel long noncoding RNA, contributes to metastasis via regulation of S100A11 in kidney renal clear cell carcinoma.LINC00997，一种新型长链非编码 RNA，通过调节肾透明细胞癌中的 S100A11 促进转移。
Int J Biochem Cell Biol. 2019 Nov;116:105590. doi: 10.1016/j.biocel.2019.105590. Epub 2019 Aug 20.
9
NUF2 Drives Clear Cell Renal Cell Carcinoma by Activating HMGA2 Transcription through KDM2A-mediated H3K36me2 Demethylation.NUF2 通过 KDM2A 介导的 H3K36me2 去甲基化激活 HMGA2 转录驱动透明细胞肾细胞癌。
Int J Biol Sci. 2022 May 16;18(9):3621-3635. doi: 10.7150/ijbs.70972. eCollection 2022.
10
Functional Long Noncoding RNAs (lncRNAs) in Clear Cell Kidney Carcinoma Revealed by Reconstruction and Comprehensive Analysis of the lncRNA-miRNA-mRNA Regulatory Network.通过构建和综合分析 lncRNA-miRNA-mRNA 调控网络揭示透明细胞肾细胞癌中的功能性长非编码 RNA（lncRNA）。
Med Sci Monit. 2018 Nov 16;24:8250-8263. doi: 10.12659/MSM.910773.

引用本文的文献

1
Lysine Methyltransferases SMYD2 and SMYD3: Emerging Targets in Kidney Diseases.赖氨酸甲基转移酶SMYD2和SMYD3：肾脏疾病中的新兴靶点
Kidney Dis (Basel). 2025 Jul 1;11(1):518-529. doi: 10.1159/000547202. eCollection 2025 Jan-Dec.
2
A novel peptide 66CTG stabilizes Myc proto-oncogene protein to promote triple-negative breast cancer growth.一种新型肽66CTG可稳定Myc原癌基因蛋白以促进三阴性乳腺癌生长。
Signal Transduct Target Ther. 2025 Jul 9;10(1):217. doi: 10.1038/s41392-025-02298-5.
3
LncRNA-Protein Interactions: A Key to Deciphering LncRNA Mechanisms.

本文引用的文献

1
LncRNA CDKN2B-AS1/miR-141/cyclin D network regulates tumor progression and metastasis of renal cell carcinoma.LncRNA CDKN2B-AS1/miR-141/cyclin D 网络调控肾细胞癌的肿瘤进展和转移。
Cell Death Dis. 2020 Aug 19;11(8):660. doi: 10.1038/s41419-020-02877-0.
2
Cancer statistics, 2020.癌症统计数据，2020 年。
CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8.
3
A novel lncRNA NR4A1AS up-regulates orphan nuclear receptor NR4A1 expression by blocking UPF1-mediated mRNA destabilization in colorectal cancer.
长链非编码RNA-蛋白质相互作用：破解长链非编码RNA机制的关键
Biomolecules. 2025 Jun 17;15(6):881. doi: 10.3390/biom15060881.
4
The role of N(6)-methyladenosine (m6a) modification in cancer: recent advances and future directions.N⁶-甲基腺苷（m⁶A）修饰在癌症中的作用：最新进展与未来方向
EXCLI J. 2025 Jan 15;24:113-150. doi: 10.17179/excli2024-7935. eCollection 2025.
5
LIN28A-dependent lncRNA NEAT1 aggravates sepsis-induced acute respiratory distress syndrome through destabilizing ACE2 mRNA by RNA methylation.LIN28A依赖的长链非编码RNA NEAT1通过RNA甲基化使ACE2信使核糖核酸不稳定，加重脓毒症诱导的急性呼吸窘迫综合征。
J Transl Med. 2025 Jan 6;23(1):15. doi: 10.1186/s12967-024-06032-7.
6
Novel insights into the interaction between IGF2BPs and ncRNAs in cancers.对癌症中IGF2BPs与非编码RNA相互作用的新见解。
Cancer Cell Int. 2024 Dec 28;24(1):437. doi: 10.1186/s12935-024-03591-z.
7
Associations of the Expression Levels and Risk Variants of CDKN2B-AS1 Long Noncoding RNA With the Susceptibility and Progression of Prostate Cancer.CDKN2B-AS1长链非编码RNA的表达水平及风险变异与前列腺癌易感性和进展的关联
J Cell Mol Med. 2024 Dec;28(23):e70264. doi: 10.1111/jcmm.70264.
8
Development of a Novel KCNN4-Related ceRNA Network and Prognostic Model for Renal Clear Cell Carcinoma.一种新型的与KCNN4相关的ceRNA网络及肾透明细胞癌预后模型的构建
Anal Cell Pathol (Amst). 2023 Jan 24;2023:2533992. doi: 10.1155/2023/2533992. eCollection 2023.
9
The role of RNA-modifying proteins in renal cell carcinoma.RNA 修饰蛋白在肾细胞癌中的作用。
Cell Death Dis. 2024 Mar 19;15(3):227. doi: 10.1038/s41419-024-06479-y.
10
LncRNA AGAP2 antisense RNA 1 stabilized by insulin-like growth factor 2 mRNA binding protein 3 promotes macrophage M2 polarization in clear cell renal cell carcinoma through regulation of the microRNA-9-5p/THBS2/PI3K-Akt pathway.由胰岛素样生长因子2信使核糖核酸结合蛋白3稳定的长链非编码RNA AGAP2反义RNA 1通过调控微小RNA-9-5p/血小板反应蛋白2/磷脂酰肌醇-3-激酶-蛋白激酶B信号通路促进透明细胞肾细胞癌中巨噬细胞的M2极化。
Cancer Cell Int. 2023 Dec 18;23(1):330. doi: 10.1186/s12935-023-03173-5.
一种新型长链非编码 RNA NR4A1AS 通过阻断 UPF1 介导的 mRNA 不稳定性上调结直肠癌中孤儿核受体 NR4A1 的表达。
Clin Sci (Lond). 2019 Jul 15;133(13):1457-1473. doi: 10.1042/CS20181061.
4
Increased IGF2BP3 expression promotes the aggressive phenotypes of colorectal cancer cells in vitro and vivo.IGF2BP3 表达增加促进结直肠癌细胞在体外和体内的侵袭表型。
J Cell Physiol. 2019 Aug;234(10):18466-18479. doi: 10.1002/jcp.28483. Epub 2019 Mar 20.
5
Circulating and tissue IMP3 levels are correlated with poor survival in renal cell carcinoma.循环和组织 IMP3 水平与肾细胞癌患者的不良预后相关。
Int J Cancer. 2019 Jul 15;145(2):531-539. doi: 10.1002/ijc.32124. Epub 2019 Jan 31.
6
Patisiran for the treatment of hereditary transthyretin-mediated amyloidosis.用于治疗遗传性转甲状腺素蛋白介导的淀粉样变性病的帕替沙那。
Expert Rev Clin Pharmacol. 2019 Feb;12(2):95-99. doi: 10.1080/17512433.2019.1567326. Epub 2019 Jan 18.
7
Exploring the mechanisms behind long noncoding RNAs and cancer.探索长链非编码RNA与癌症背后的机制。
Noncoding RNA Res. 2018 Mar 31;3(3):108-117. doi: 10.1016/j.ncrna.2018.03.001. eCollection 2018 Sep.
8
: A lncRNA at the CDKN2A/B Locus With Roles in Cancer and Metabolic Disease.CDKN2A/B基因座处的一个lncRNA在癌症和代谢性疾病中的作用
Front Endocrinol (Lausanne). 2018 Jul 24;9:405. doi: 10.3389/fendo.2018.00405. eCollection 2018.
9
Truncated Isoforms of lncRNA ANRIL Are Overexpressed in Bladder Cancer, But Do Not Contribute to Repression of INK4 Tumor Suppressors.lncRNA ANRIL的截短异构体在膀胱癌中过表达，但对INK4肿瘤抑制因子的抑制作用无贡献。
Noncoding RNA. 2015 Dec 17;1(3):266-284. doi: 10.3390/ncrna1030266.
10
The LINC01138 drives malignancies via activating arginine methyltransferase 5 in hepatocellular carcinoma.LINC01138 通过激活肝癌中的精氨酸甲基转移酶 5 来驱动恶性肿瘤。
Nat Commun. 2018 Apr 20;9(1):1572. doi: 10.1038/s41467-018-04006-0.