• 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PRDM2通过海绵化miR-760提高EZH2水平促进骨肉瘤对多柔比星的耐药性。

CircPRDM2 Contributes to Doxorubicin Resistance of Osteosarcoma by Elevating EZH2 via Sponging miR-760.

作者信息

Yuan Jianjun, Liu Yan, Zhang Quan, Ren Zhishuai, Li Guang, Tian Rong

机构信息

Department of Spine Surgery, Tianjin Union Medical Center, Tianjin, 300121, People's Republic of China.

出版信息

Cancer Manag Res. 2021 Jun 2;13:4433-4445. doi: 10.2147/CMAR.S295147. eCollection 2021.

DOI:10.2147/CMAR.S295147
PMID:34103997
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8180268/
Abstract

BACKGROUND

Circular RNAs (circRNAs) are implicated in the chemoresistance of human cancers. However, the functions of circRNA PR/SET domain 2 (circPRDM2) in the resistance of osteosarcoma (OS) to doxorubicin (DXR) are unknown.

METHODS

Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted to determine the levels of circPRDM2, microRNA-760 (miR-760) and enhancer of zeste homolog 2 (EZH2). RNase R assay was used to analyze the characteristics of circPRDM2. IC50 of DXR was estimated by Cell Counting Kit-8 (CCK-8) assay. Colony formation assay was performed for cell colony formation ability. Wound-healing assay and transwell assay were utilized for cell migration and invasion. Flow cytometry analysis was conducted for cell apoptosis. Western blot assay was employed for protein levels. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay were adopted to analyze the relationships among circPRDM2, miR-760 and EZH2. Murine xenograft model assay was utilized to explore DXR resistance in vivo.

RESULTS

CircPRDM2 level was enhanced in DXR-resistant OS tissues and cells. CircPRDM2 deficiency inhibited IC50 of DXR, colony formation, migration and invasion and facilitated apoptosis in DXR-resistant OS cells in vitro. CircPRDM2 was identified as the sponge for miR-760. MiR-760 inhibition reversed the inhibitory effects of circPRDM2 knockdown on DXR resistance and cell progression in DXR-resistant OS cells. Moreover, EZH2 was identified as the target gene of miR-760 and EZH2 overexpression abolished miR-760-mediated impacts on DXR sensitivity and malignant behaviors in DXR-resistant OS cells. Also, circPRDM2 silencing improved DXR sensitivity in vivo.

CONCLUSION

Our study demonstrated the role of circPRDM2/miR-760/EZH2 axis in enhancing DXR resistance.

摘要

背景

环状RNA（circRNA）与人类癌症的化疗耐药性有关。然而，环状PR/SET结构域2（circPRDM2）在骨肉瘤（OS）对阿霉素（DXR）耐药中的作用尚不清楚。

方法

采用定量实时聚合酶链反应（qRT-PCR）检测circPRDM2、微小RNA-760（miR-760）和zeste同源物2增强子（EZH2）的水平。用核糖核酸酶R检测分析circPRDM2的特征。采用细胞计数试剂盒-8（CCK-8）检测法评估DXR的半数抑制浓度（IC50）。进行集落形成试验以检测细胞集落形成能力。采用伤口愈合试验和Transwell试验检测细胞迁移和侵袭能力。通过流式细胞术分析细胞凋亡情况。采用蛋白质免疫印迹法检测蛋白质水平。采用双荧光素酶报告基因检测、RNA免疫沉淀（RIP）检测和RNA下拉检测分析circPRDM2、miR-760和EZH2之间的关系。利用小鼠异种移植模型试验在体内探索DXR耐药性。

结果

circPRDM2水平在DXR耐药的OS组织和细胞中升高。circPRDM2缺陷抑制了DXR的IC50、集落形成、迁移和侵袭，并促进了体外DXR耐药OS细胞的凋亡。circPRDM2被鉴定为miR-760的海绵。抑制miR-760可逆转circPRDM2敲低对DXR耐药OS细胞中DXR耐药性和细胞进展的抑制作用。此外，EZH2被鉴定为miR-760的靶基因，EZH2过表达消除了miR-760介导的对DXR耐药OS细胞中DXR敏感性和恶性行为的影响。此外，circPRDM2沉默可提高体内DXR敏感性。

结论

我们的研究证明了circPRDM2/miR-760/EZH2轴在增强DXR耐药性中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/73c5663652dd/CMAR-13-4433-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/e103981a5a4c/CMAR-13-4433-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/8251a0914080/CMAR-13-4433-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/c0eb24b5659a/CMAR-13-4433-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/8defde87b34a/CMAR-13-4433-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/3a6cbaf0d0c0/CMAR-13-4433-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/8ab028fd0bba/CMAR-13-4433-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/73c5663652dd/CMAR-13-4433-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/e103981a5a4c/CMAR-13-4433-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/8251a0914080/CMAR-13-4433-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/c0eb24b5659a/CMAR-13-4433-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/8defde87b34a/CMAR-13-4433-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/3a6cbaf0d0c0/CMAR-13-4433-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/8ab028fd0bba/CMAR-13-4433-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71c3/8180268/73c5663652dd/CMAR-13-4433-g0007.jpg

相似文献

1
CircPRDM2 Contributes to Doxorubicin Resistance of Osteosarcoma by Elevating EZH2 via Sponging miR-760.环状PRDM2通过海绵化miR-760提高EZH2水平促进骨肉瘤对多柔比星的耐药性。
Cancer Manag Res. 2021 Jun 2;13:4433-4445. doi: 10.2147/CMAR.S295147. eCollection 2021.
2
Circular RNA hsa_circ_0003496 Contributes to Tumorigenesis and Chemoresistance in Osteosarcoma Through Targeting (microRNA) miR-370/Krüppel-Like Factor 12 Axis.环状RNA hsa_circ_0003496通过靶向（微小RNA）miR-370/类 Kruppel 样因子12轴促进骨肉瘤的肿瘤发生和化疗耐药。
Cancer Manag Res. 2020 Sep 9;12:8229-8240. doi: 10.2147/CMAR.S253969. eCollection 2020.
3
Circular RNA_ANKIB1 accelerates chemo-resistance of osteosarcoma via binding microRNA-26b-5p and modulating enhancer of zeste homolog 2.环状 RNA_ANKIB1 通过结合 microRNA-26b-5p 并调节增强子结合蛋白 2 来加速骨肉瘤的化疗耐药性。
Bioengineered. 2022 Mar;13(3):7351-7366. doi: 10.1080/21655979.2022.2037869.
4
Hsa_circ_0004674 promotes osteosarcoma doxorubicin resistance by regulating the miR-342-3p/FBN1 axis.Hsa_circ_0004674 通过调控 miR-342-3p/FBN1 轴促进骨肉瘤多柔比星耐药。
J Orthop Surg Res. 2021 Aug 18;16(1):510. doi: 10.1186/s13018-021-02631-y.
5
Circ_0001721 enhances doxorubicin resistance and promotes tumorigenesis in osteosarcoma through miR-758/TCF4 axis.Circ_0001721通过miR-758/TCF4轴增强骨肉瘤对多柔比星的耐药性并促进肿瘤发生。
Cancer Cell Int. 2021 Jul 2;21(1):336. doi: 10.1186/s12935-021-02016-5.
6
Down-regulation of circITCH promotes osteosarcoma development and resistance to doxorubicin via the miR-524/RASSF6 axis.环状 RNA ITCH 通过 miR-524/RASSF6 轴下调促进骨肉瘤的发展和对阿霉素的耐药性。
J Gene Med. 2021 Oct;23(10):e3373. doi: 10.1002/jgm.3373. Epub 2021 Jul 20.
7
Circular RNA circPVT1 Contributes to Doxorubicin (DXR) Resistance of Osteosarcoma Cells by Regulating TRIAP1 via miR-137.环状RNA circPVT1通过miR-137调控TRIAP1促进骨肉瘤细胞对多柔比星（DXR）的耐药性。
Biomed Res Int. 2021 Apr 23;2021:7463867. doi: 10.1155/2021/7463867. eCollection 2021.
8
CircSAMD4A contributes to cell doxorubicin resistance in osteosarcoma by regulating the miR-218-5p/KLF8 axis.环状SAMD4A通过调控miR-218-5p/KLF8轴促进骨肉瘤细胞对阿霉素的耐药性。
Open Life Sci. 2020 Nov 24;15(1):848-859. doi: 10.1515/biol-2020-0079. eCollection 2020.
9
CircARVCF Contributes to Cisplatin Resistance in Gastric Cancer by Altering miR-1205 and FGFR1.环状 ARVCF 通过改变 miR-1205 和 FGFR1 促进胃癌顺铂耐药。
Front Genet. 2021 Nov 25;12:767590. doi: 10.3389/fgene.2021.767590. eCollection 2021.
10
CircRFX3 contributes to glioma progression through the circRFX3-miR-1179/miR-1229-VASP axis.环状RNA RFX3通过环状RNA RFX3- miR-1179/miR-1229-血管舒张刺激磷蛋白轴促进胶质瘤进展。
Cancer Cell Int. 2021 Nov 2;21(1):588. doi: 10.1186/s12935-021-02293-0.

引用本文的文献

1
Treating human cancer by targeting EZH2.通过靶向EZH2治疗人类癌症。
Genes Dis. 2024 Apr 25;12(3):101313. doi: 10.1016/j.gendis.2024.101313. eCollection 2025 May.
2
Research progress of circRNAs in bone-related diseases.环状RNA在骨相关疾病中的研究进展
Front Oncol. 2025 Jan 27;15:1481322. doi: 10.3389/fonc.2025.1481322. eCollection 2025.
3
Therapeutic targeting potential of the protein lysine and arginine methyltransferases to reverse cancer chemoresistance.蛋白质赖氨酸和精氨酸甲基转移酶逆转癌症化疗耐药性的治疗靶向潜力。

本文引用的文献

1
LncRNA ANRIL Regulates Ovarian Cancer Progression and Tumor Stem Cell-Like Characteristics via miR-324-5p/Ran Axis.长链非编码RNA ANRIL通过miR-324-5p/Ran轴调控卵巢癌进展及肿瘤干细胞样特征。
Onco Targets Ther. 2021 Jan 19;14:565-576. doi: 10.2147/OTT.S273614. eCollection 2021.
2
MicroRNA-200c Nanoparticles Sensitized Gastric Cancer Cells to Radiotherapy by Regulating PD-L1 Expression and EMT.微小RNA-200c纳米颗粒通过调节程序性死亡配体1（PD-L1）表达和上皮-间质转化使胃癌细胞对放疗敏感。
Cancer Manag Res. 2020 Nov 27;12:12215-12223. doi: 10.2147/CMAR.S279978. eCollection 2020.
3
MicroRNA‑487b‑3p inhibits osteosarcoma chemoresistance and metastasis by targeting ALDH1A3.
Front Mol Biosci. 2024 Dec 5;11:1455415. doi: 10.3389/fmolb.2024.1455415. eCollection 2024.
4
The role of circRNAs in resistance to doxorubicin.环状 RNA 在对抗阿霉素耐药中的作用。
Cell Commun Signal. 2024 Nov 29;22(1):572. doi: 10.1186/s12964-024-01952-9.
5
Osteosarcoma in a ceRNET perspective.中枢神经系统外尤文肉瘤的临床特征。
J Biomed Sci. 2024 Jun 5;31(1):59. doi: 10.1186/s12929-024-01049-y.
6
miRNAs as short non-coding RNAs in regulating doxorubicin resistance.微小RNA作为短链非编码RNA在调节阿霉素耐药性中的作用
J Cell Commun Signal. 2023 Dec;17(4):1181-1202. doi: 10.1007/s12079-023-00789-0. Epub 2023 Nov 29.
7
The strategy and clinical relevance of in vitro models of MAP resistance in osteosarcoma: a systematic review.体外模型在骨肉瘤耐多药研究中的策略和临床相关性：系统综述。
Oncogene. 2023 Jan;42(4):259-277. doi: 10.1038/s41388-022-02529-x. Epub 2022 Nov 25.
8
An overview of resistance to chemotherapy in osteosarcoma and future perspectives.骨肉瘤化疗耐药概述及未来展望。
Cancer Drug Resist. 2022 Jun 23;5(3):762-793. doi: 10.20517/cdr.2022.18. eCollection 2022.
9
Advances in the Study of CircRNAs in Tumor Drug Resistance.环状RNA在肿瘤耐药性研究中的进展
Front Oncol. 2022 May 9;12:868363. doi: 10.3389/fonc.2022.868363. eCollection 2022.
10
Circular RNA_ANKIB1 accelerates chemo-resistance of osteosarcoma via binding microRNA-26b-5p and modulating enhancer of zeste homolog 2.环状 RNA_ANKIB1 通过结合 microRNA-26b-5p 并调节增强子结合蛋白 2 来加速骨肉瘤的化疗耐药性。
Bioengineered. 2022 Mar;13(3):7351-7366. doi: 10.1080/21655979.2022.2037869.
miR-487b-3p 通过靶向 ALDH1A3 抑制骨肉瘤化疗耐药和转移。
Oncol Rep. 2020 Dec;44(6):2691-2700. doi: 10.3892/or.2020.7814. Epub 2020 Oct 19.
4
Up-Regulation of circRNA hsa_circ_0003074 Expression is a Reliable Diagnostic and Prognostic Biomarker in Patients with Osteosarcoma.环状RNA hsa_circ_0003074表达上调是骨肉瘤患者可靠的诊断和预后生物标志物。
Cancer Manag Res. 2020 Sep 29;12:9315-9325. doi: 10.2147/CMAR.S262093. eCollection 2020.
5
Circ_0007031 Serves as a Sponge of miR-760 to Regulate the Growth and Chemoradiotherapy Resistance of Colorectal Cancer via Regulating DCP1A.环状RNA_0007031作为miR-760的海绵，通过调控DCP1A来调节结直肠癌的生长和放化疗耐药性。
Cancer Manag Res. 2020 Sep 14;12:8465-8479. doi: 10.2147/CMAR.S254815. eCollection 2020.
6
Circular RNA hsa_circ_0003496 Contributes to Tumorigenesis and Chemoresistance in Osteosarcoma Through Targeting (microRNA) miR-370/Krüppel-Like Factor 12 Axis.环状RNA hsa_circ_0003496通过靶向（微小RNA）miR-370/类 Kruppel 样因子12轴促进骨肉瘤的肿瘤发生和化疗耐药。
Cancer Manag Res. 2020 Sep 9;12:8229-8240. doi: 10.2147/CMAR.S253969. eCollection 2020.
7
Circular RNA hsa_circ_0000073 contributes to osteosarcoma cell proliferation, migration, invasion and methotrexate resistance by sponging miR-145-5p and miR-151-3p and upregulating NRAS.环状 RNA hsa_circ_0000073 通过海绵吸附 miR-145-5p 和 miR-151-3p 并上调 NRAS 促进骨肉瘤细胞增殖、迁移、侵袭和耐甲氨蝶呤。
Aging (Albany NY). 2020 Jul 24;12(14):14157-14173. doi: 10.18632/aging.103423.
8
Long Non-Coding RNA ASB16-AS1 Functions as a miR-760 Sponge to Facilitate the Malignant Phenotype of Osteosarcoma by Increasing HDGF Expression.长链非编码RNA ASB16-AS1作为miR-760的海绵，通过增加HDGF表达促进骨肉瘤的恶性表型。
Onco Targets Ther. 2020 Mar 13;13:2261-2274. doi: 10.2147/OTT.S240022. eCollection 2020.
9
MicroRNA-760 inhibits cell viability and migration through down-regulating BST2 in gastric cancer.MicroRNA-760 通过下调胃癌中的 BST2 抑制细胞活力和迁移。
J Biochem. 2020 Aug 1;168(2):159-170. doi: 10.1093/jb/mvaa031.
10
MiR-760 enhances sensitivity of pancreatic cancer cells to gemcitabine through modulating Integrin β1.miR-760 通过调节整合素 β1 增强胰腺癌对吉西他滨的敏感性。
Biosci Rep. 2019 Nov 29;39(11). doi: 10.1042/BSR20192358.