• 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

单核苷酸多态性介导的长链非编码 RNA-ENTPD3-AS1 上调通过 miR-155/HIF-1α 信号通路抑制肾细胞癌。

SNP-mediated lncRNA-ENTPD3-AS1 upregulation suppresses renal cell carcinoma via miR-155/HIF-1α signaling.

机构信息

Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China.

Department of Urology, Jinling Hospital, Medical School, Nanjing University, Nanjing, China.

出版信息

Cell Death Dis. 2021 Jul 3;12(7):672. doi: 10.1038/s41419-021-03958-4.

DOI:10.1038/s41419-021-03958-4
PMID:34218253
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8254807/
Abstract

Over the last decade, more than 10 independent SNPs have been discovered to be associated with the risk of renal cell carcinoma among different populations. However, the biological functions of them remain poorly understood. In this study, we performed eQTL analysis, ChIP-PCR, luciferase reporter assay, and Cox regression analysis to identify the functional role and underlying mechanism of rs67311347 in RCC. The ENCORI database, which contains the lncRNA-miRNA-mRNA interactions, was used to explore the possible target miRNA of ENTPD3-AS1. The results showed that the G > A mutation of rs67311347 created a binding motif of ZNF8 and subsequently upregulated ENTPD3-AS1 expression by acting as an enhancer. The TCGA-KIRC and our cohorts both confirmed the downregulation of ENTPD3-AS1 in RCC tissues and demonstrated that increased ENTPD3-AS1 expression was associated with good OS and PFS. Furthermore, ENTPD3-AS1 interacted with miR-155-5p and activated the expression of HIF-1α, which was an important tumor suppressor gene in the development of RCC. The functional experiments revealed that overexpression of ENTPD3-AS1 inhibited cell proliferation in RCC cell lines and the effect could be rescued by knocking down HIF-1α. Our findings reveal that SNP-mediated lncRNA-ENTPD3-AS1 upregulation suppresses renal cell carcinoma via miR-155/HIF-1α signaling.

摘要

在过去的十年中，已经发现了 10 多个独立的单核苷酸多态性（SNP）与不同人群的肾细胞癌风险相关。然而，它们的生物学功能仍知之甚少。在这项研究中，我们进行了 eQTL 分析、ChIP-PCR、荧光素酶报告基因检测和 Cox 回归分析，以确定 rs67311347 在肾细胞癌中的功能作用和潜在机制。ENCORI 数据库包含 lncRNA-miRNA-mRNA 相互作用，用于探索 ENTPD3-AS1 的可能靶 miRNA。结果表明，rs67311347 的 G>A 突变创造了 ZNF8 的结合基序，并通过充当增强子来上调 ENTPD3-AS1 的表达。TCGA-KIRC 和我们的队列都证实了 ENTPD3-AS1 在肾细胞癌组织中的下调，并表明 ENTPD3-AS1 表达的增加与良好的 OS 和 PFS 相关。此外，ENTPD3-AS1 与 miR-155-5p 相互作用并激活 HIF-1α 的表达，HIF-1α 是肾细胞癌发生的重要肿瘤抑制基因。功能实验表明，ENTPD3-AS1 的过表达抑制肾癌细胞系中的细胞增殖，并且通过敲低 HIF-1α可以挽救这种作用。我们的研究结果表明，SNP 介导的 lncRNA-ENTPD3-AS1 上调通过 miR-155/HIF-1α 信号通路抑制肾细胞癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c952/8254807/c8a8411c4a46/41419_2021_3958_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c952/8254807/a7a336ac7ac6/41419_2021_3958_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c952/8254807/e6c4e0e98071/41419_2021_3958_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c952/8254807/cdd8f07725ea/41419_2021_3958_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c952/8254807/aef5d116e2e2/41419_2021_3958_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c952/8254807/b8c11312590a/41419_2021_3958_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c952/8254807/c8a8411c4a46/41419_2021_3958_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c952/8254807/a7a336ac7ac6/41419_2021_3958_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c952/8254807/e6c4e0e98071/41419_2021_3958_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c952/8254807/cdd8f07725ea/41419_2021_3958_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c952/8254807/aef5d116e2e2/41419_2021_3958_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c952/8254807/b8c11312590a/41419_2021_3958_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c952/8254807/c8a8411c4a46/41419_2021_3958_Fig6_HTML.jpg

相似文献

1
SNP-mediated lncRNA-ENTPD3-AS1 upregulation suppresses renal cell carcinoma via miR-155/HIF-1α signaling.单核苷酸多态性介导的长链非编码 RNA-ENTPD3-AS1 上调通过 miR-155/HIF-1α 信号通路抑制肾细胞癌。
Cell Death Dis. 2021 Jul 3;12(7):672. doi: 10.1038/s41419-021-03958-4.
2
Long non-conding RNA LOXL1-AS1 sponges miR-589-5p to up-regulate CBX5 expression in renal cell carcinoma.长非编码 RNA LOXL1-AS1 通过海绵吸附 miR-589-5p 上调肾细胞癌中 CBX5 的表达。
Biosci Rep. 2020 Nov 27;40(11). doi: 10.1042/BSR20200212.
3
LncRNA HOTAIR regulates HIF-1α/AXL signaling through inhibition of miR-217 in renal cell carcinoma.长链非编码RNA HOTAIR通过抑制miR-217调控肾细胞癌中的HIF-1α/AXL信号通路。
Cell Death Dis. 2017 May 11;8(5):e2772. doi: 10.1038/cddis.2017.181.
4
LncRNA DLX6-AS1 increases the expression of HIF-1α and promotes the malignant phenotypes of nasopharyngeal carcinoma cells via targeting MiR-199a-5p.长链非编码 RNA DLX6-AS1 通过靶向 miR-199a-5p 增加 HIF-1α 的表达，促进鼻咽癌细胞的恶性表型。
Mol Genet Genomic Med. 2020 Jan;8(1):e1017. doi: 10.1002/mgg3.1017. Epub 2019 Nov 29.
5
Long noncoding RNA ZFPM2-AS1 promotes the tumorigenesis of renal cell cancer via targeting miR-137.长链非编码 RNA ZFPM2-AS1 通过靶向 miR-137 促进肾细胞癌的肿瘤发生。
Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5675-5681. doi: 10.26355/eurrev_201907_18304.
6
LncRNA FGD5-AS1/miR-5590-3p axis facilitates the proliferation and metastasis of renal cell carcinoma through ERK/AKT signalling.长链非编码RNA FGD5-AS1/微小RNA-5590-3p轴通过ERK/AKT信号通路促进肾细胞癌的增殖和转移。
Eur Rev Med Pharmacol Sci. 2020 Sep;24(17):8756-8766. doi: 10.26355/eurrev_202009_22814.
7
LncRNA TMPO-AS1 up-regulates the expression of HIF-1α and promotes the malignant phenotypes of retinoblastoma cells via sponging miR-199a-5p.长链非编码 RNA TMPO-AS1 通过海绵吸附 miR-199a-5p 上调 HIF-1α 的表达，促进视网膜母细胞瘤细胞的恶性表型。
Pathol Res Pract. 2020 Apr;216(4):152853. doi: 10.1016/j.prp.2020.152853. Epub 2020 Feb 5.
8
Long non-coding RNA VCAN-AS1 promotes the malignant behaviors of breast cancer by regulating the miR-106a-5p-mediated STAT3/HIF-1α pathway.长链非编码 RNA VCAN-AS1 通过调控 miR-106a-5p 介导的 STAT3/HIF-1α 通路促进乳腺癌的恶性行为。
Bioengineered. 2021 Dec;12(1):5028-5044. doi: 10.1080/21655979.2021.1960774.
9
DARS-AS1 promotes clear cell renal cell carcinoma by sequestering miR-194-5p to up-regulate DARS.DARS-AS1 通过隔离 miR-194-5p 来上调 DARS 促进肾透明细胞癌。
Biomed Pharmacother. 2020 Aug;128:110323. doi: 10.1016/j.biopha.2020.110323. Epub 2020 Jun 8.
10
The long non-coding RNA NNT-AS1 promotes clear cell renal cell carcinoma progression via regulation of the miR-137/ Y-box binding protein 1 axis.长链非编码 RNA NNT-AS1 通过调节 miR-137/Y 盒结合蛋白 1 轴促进肾透明细胞癌的进展。
Bioengineered. 2021 Dec;12(1):8994-9005. doi: 10.1080/21655979.2021.1992330.

引用本文的文献

1
Multi-omics integration reveals the role of N6-methyladenosine in epilepsy, ischemic stroke, and vascular dementia.多组学整合揭示了N6-甲基腺苷在癫痫、缺血性中风和血管性痴呆中的作用。
Mol Brain. 2025 Jul 7;18(1):58. doi: 10.1186/s13041-025-01228-4.
2
Correlation study of LINC02609 and SNHG17 as prognostic biomarkers of kidney renal clear cell carcinoma and therapeutic sensitivity based on public data and analysis.基于公开数据和分析的LINC02609和SNHG17作为肾透明细胞癌预后生物标志物及治疗敏感性的相关性研究
Front Immunol. 2025 May 26;16:1592474. doi: 10.3389/fimmu.2025.1592474. eCollection 2025.
3
Dual role of miR-155 and exosomal miR-155 in tumor angiogenesis: implications for cancer progression and therapy.

本文引用的文献

1
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.
2
Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial.派姆单抗联合阿昔替尼对比舒尼替尼作为晚期肾细胞癌的一线治疗（KEYNOTE-426）：一项随机、开放标签、III 期试验的延长随访。
Lancet Oncol. 2020 Dec;21(12):1563-1573. doi: 10.1016/S1470-2045(20)30436-8. Epub 2020 Oct 23.
3
Genomic profiling in renal cell carcinoma.
miR-155和外泌体miR-155在肿瘤血管生成中的双重作用：对癌症进展和治疗的影响
Eur J Med Res. 2025 May 19;30(1):393. doi: 10.1186/s40001-025-02618-z.
4
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.
5
Unlocking the Potential of Disulfidptosis-Related LncRNAs in Lung Adenocarcinoma: A Promising Prognostic LncRNA Model for Survival and Immunotherapy Prediction.解锁肺腺癌中与二硫键相关的长链非编码 RNA 的潜力：一个有前途的用于生存和免疫治疗预测的长链非编码 RNA 模型。
Cancer Med. 2024 Oct;13(20):e70337. doi: 10.1002/cam4.70337.
6
Exosome in renal cell carcinoma progression and implications for targeted therapy.外泌体在肾细胞癌进展中的作用及对靶向治疗的意义。
Front Oncol. 2024 Sep 4;14:1458616. doi: 10.3389/fonc.2024.1458616. eCollection 2024.
7
Prevention and treatment of peri-implant fibrosis by functionally inhibiting skeletal cells expressing the leptin receptor.通过功能抑制表达瘦素受体的成骨细胞来预防和治疗种植体周围纤维化。
Nat Biomed Eng. 2024 Oct;8(10):1285-1307. doi: 10.1038/s41551-024-01238-y. Epub 2024 Jul 31.
8
Identification of miRNAs and Their Target Genes Associated with Sunitinib Resistance in Clear Cell Renal Cell Carcinoma Patients.鉴定与舒尼替尼耐药相关的微小 RNA 及其靶基因在透明细胞肾细胞癌患者中的作用。
Int J Mol Sci. 2024 Jun 22;25(13):6881. doi: 10.3390/ijms25136881.
9
Integrated Bioinformatics and Experimental Validation to Identify a Disulfidptosis-Related lncRNA Model for Prognostic Prediction in Papillary Renal Cell Carcinoma.整合生物信息学与实验验证以鉴定用于乳头状肾细胞癌预后预测的二硫化物化相关lncRNA模型
Comb Chem High Throughput Screen. 2025;28(5):883-898. doi: 10.2174/0113862073303084240403051346.
10
Exosomes in renal cell carcinoma: challenges and opportunities.肾细胞癌中的细胞外囊泡：挑战与机遇。
Mol Biol Rep. 2024 Mar 23;51(1):443. doi: 10.1007/s11033-024-09384-x.
肾细胞癌的基因组分析。
Nat Rev Nephrol. 2020 Aug;16(8):435-451. doi: 10.1038/s41581-020-0301-x. Epub 2020 Jun 19.
4
Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma.JAVELIN肾101试验的最新疗效结果：一线阿维鲁单抗联合阿昔替尼与舒尼替尼治疗晚期肾细胞癌患者的对比
Ann Oncol. 2020 Aug;31(8):1030-1039. doi: 10.1016/j.annonc.2020.04.010. Epub 2020 Apr 25.
5
An exome-wide rare variant analysis of Korean men identifies three novel genes predisposing to prostate cancer.韩国男性外显子组稀有变异分析确定了三个导致前列腺癌的新易感基因。
Sci Rep. 2019 Nov 20;9(1):17173. doi: 10.1038/s41598-019-53445-2.
6
A 16q22.1 variant confers susceptibility to colorectal cancer as a distal regulator of ZFP90.一个位于 16q22.1 的变异可作为 ZFP90 的远端调控因子增加结直肠癌的易感性。
Oncogene. 2020 Feb;39(6):1347-1360. doi: 10.1038/s41388-019-1055-4. Epub 2019 Oct 22.
7
Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.阿维鲁单抗联合阿昔替尼与舒尼替尼治疗晚期肾细胞癌。
N Engl J Med. 2019 Mar 21;380(12):1103-1115. doi: 10.1056/NEJMoa1816047. Epub 2019 Feb 16.
8
Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.派姆单抗联合阿昔替尼对比舒尼替尼用于晚期肾细胞癌。
N Engl J Med. 2019 Mar 21;380(12):1116-1127. doi: 10.1056/NEJMoa1816714. Epub 2019 Feb 16.
9
Genetic Predisposition to Renal Cell Carcinoma: Implications for Counseling, Testing, Screening, and Management.肾细胞癌的遗传易感性：对咨询、检测、筛查及管理的意义
J Clin Oncol. 2018 Oct 29:JCO2018792523. doi: 10.1200/JCO.2018.79.2523.
10
Risk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19.风险 SNP 介导的启动子-增强子转换通过 lncRNA PCAT19 驱动前列腺癌。
Cell. 2018 Jul 26;174(3):564-575.e18. doi: 10.1016/j.cell.2018.06.014. Epub 2018 Jul 19.