• 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

miR-486-5p的下调增强了5-氟尿嘧啶对胰腺癌细胞的抗肿瘤作用。

Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells.

作者信息

Wang Wei, Liu Bowei, Sun Suofeng, Lan Ling, Chen Yu, Han Shuangyin, Li Xiuling, Li Zhaoshen

机构信息

Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai 200433, People's Republic of China.

Department of Gastroenterology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan 450003, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Feb 24;13:1649-1659. doi: 10.2147/OTT.S231153. eCollection 2020.

DOI:10.2147/OTT.S231153
PMID:32158231
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7047986/
Abstract

BACKGROUND

5-Fluorouracil (5-Fu) has been applied to treat pancreatic cancer, which is one of the most common types of digestive system tumors. Evidence has shown that miR-486-5p could promote the proliferation of pancreatic cancer cells. Therefore, this study aimed to investigate whether downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells.

METHODS

Cell Counting Kit 8 assay, flow cytometry and wound healing assays were used to detect proliferation, apoptosis and migration in PANC-1 cells. The expressions of Bcl-2, Bax, cleaved caspase 3, PTEN, p-Akt and p-ERK in PANC-1 cells were detected with Western blot assay.

RESULTS

In this study, the inhibitory effects of 5-Fu on the proliferation, migration and invasion of PANC-1 cells were significantly enhanced following transfection with miR-486-5p antagonist. In addition, downregulation of miR-486-5p markedly enhanced the pro-apoptosis effect of 5-Fu on PANC-1 cells. Moreover, bioinformatics analysis and luciferase reporter assay identified that PTEN was the directly binding target of miR-486-5p. Meanwhile, downregulation of miR-486-5p markedly enhanced the anti-tumor effect of 5-Fu in PANC-1 cells via upregulation of the level of PTEN, and downregulation of the expressions of p-ERK and p-Akt. In vivo experiments confirmed that knockdown of miR-486-5p could enhance the anti-tumor effect of 5-Fu in PANC-1 xenograft model.

CONCLUSION

We found that the downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells. Therefore, miR-486-5p antagonist plus 5-Fu might be considered as a potential therapeutic strategy for the treatment of pancreatic cancer.

摘要

背景

5-氟尿嘧啶（5-Fu）已被应用于治疗胰腺癌，胰腺癌是消化系统最常见的肿瘤类型之一。有证据表明，miR-486-5p可促进胰腺癌细胞的增殖。因此，本研究旨在探讨下调miR-486-5p是否能增强5-Fu对胰腺癌细胞的抗肿瘤作用。

方法

采用细胞计数试剂盒8检测、流式细胞术和伤口愈合试验检测PANC-1细胞的增殖、凋亡和迁移情况。用蛋白质免疫印迹法检测PANC-1细胞中Bcl-2、Bax、裂解的半胱天冬酶3、PTEN、p-Akt和p-ERK的表达。

结果

在本研究中，用miR-486-5p拮抗剂转染后，5-Fu对PANC-1细胞增殖、迁移和侵袭的抑制作用显著增强。此外，miR-486-5p的下调显著增强了5-Fu对PANC-1细胞的促凋亡作用。此外，生物信息学分析和荧光素酶报告基因检测确定PTEN是miR-486-5p的直接结合靶点。同时，miR-486-5p的下调通过上调PTEN水平、下调p-ERK和p-Akt的表达，显著增强了5-Fu对PANC-1细胞的抗肿瘤作用。体内实验证实，敲低miR-486-5p可增强5-Fu在PANC-1异种移植模型中的抗肿瘤作用。

结论

我们发现下调miR-486-5p可增强5-Fu对胰腺癌细胞的抗肿瘤作用。因此，miR-486-5p拮抗剂联合5-Fu可能被认为是治疗胰腺癌的一种潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d20/7047986/daefd5825203/OTT-13-1649-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d20/7047986/e47abab60267/OTT-13-1649-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d20/7047986/fbd5ae5533ec/OTT-13-1649-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d20/7047986/98f0f5855f0c/OTT-13-1649-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d20/7047986/c88ba85d84d3/OTT-13-1649-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d20/7047986/b6af4f6d9a58/OTT-13-1649-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d20/7047986/daefd5825203/OTT-13-1649-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d20/7047986/e47abab60267/OTT-13-1649-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d20/7047986/fbd5ae5533ec/OTT-13-1649-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d20/7047986/98f0f5855f0c/OTT-13-1649-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d20/7047986/c88ba85d84d3/OTT-13-1649-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d20/7047986/b6af4f6d9a58/OTT-13-1649-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d20/7047986/daefd5825203/OTT-13-1649-g0006.jpg

相似文献

1
Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells.miR-486-5p的下调增强了5-氟尿嘧啶对胰腺癌细胞的抗肿瘤作用。
Onco Targets Ther. 2020 Feb 24;13:1649-1659. doi: 10.2147/OTT.S231153. eCollection 2020.
2
Downregulation of miR-183 inhibits the growth of PANC-1 pancreatic cancer cells and , and increases chemosensitivity to 5-fluorouracil and gemcitabine.miR-183的下调抑制了PANC-1胰腺癌细胞的生长，并增加了对5-氟尿嘧啶和吉西他滨的化疗敏感性。
Exp Ther Med. 2019 Mar;17(3):1697-1705. doi: 10.3892/etm.2018.7112. Epub 2018 Dec 19.
3
MiR-139-5p/SLC7A11 inhibits the proliferation, invasion and metastasis of pancreatic carcinoma via PI3K/Akt signaling pathway.miR-139-5p/SLC7A11 通过 PI3K/Akt 信号通路抑制胰腺癌的增殖、侵袭和转移。
Biochim Biophys Acta Mol Basis Dis. 2020 Jun 1;1866(6):165747. doi: 10.1016/j.bbadis.2020.165747. Epub 2020 Feb 26.
4
CircDDX17 reduces 5-fluorouracil resistance and hinders tumorigenesis in colorectal cancer by regulating miR-31-5p/KANK1 axis.环状 RNA DDX17 通过调控 miR-31-5p/KANK1 轴降低结直肠癌对 5-氟尿嘧啶的耐药性并抑制肿瘤发生。
Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):1743-1754. doi: 10.26355/eurrev_202002_20351.
5
MiR-153-5p Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to Paclitaxel by Inducing G2M Phase Arrest.MiR-153-5p通过诱导G2M期阻滞增强三阴性乳腺癌细胞对紫杉醇的敏感性。
Onco Targets Ther. 2020 May 12;13:4089-4097. doi: 10.2147/OTT.S241640. eCollection 2020.
6
Syndecan-2, negatively regulated by miR-20b-5p, contributes to 5-fluorouracil resistance of colorectal cancer cells via the JNK/ERK signaling pathway.硫酸乙酰肝素蛋白聚糖 2 通过调控 miR-20b-5p 的表达促进结直肠癌细胞对 5-氟尿嘧啶的耐药性及其作用机制的研究
Acta Biochim Biophys Sin (Shanghai). 2021 Nov 10;53(11):1547-1557. doi: 10.1093/abbs/gmab124.
7
miR-509-5p inhibits cellular proliferation and migration via targeting MDM2 in pancreatic cancer cells.miR-509-5p通过靶向胰腺癌细胞中的MDM2抑制细胞增殖和迁移。
Onco Targets Ther. 2017 Sep 11;10:4455-4464. doi: 10.2147/OTT.S130378. eCollection 2017.
8
Simultaneous microRNA-612 restoration and 5-FU treatment inhibit the growth and migration of human PANC-1 pancreatic cancer cells.同时进行微小RNA-612恢复和5-氟尿嘧啶治疗可抑制人PANC-1胰腺癌细胞的生长和迁移。
EXCLI J. 2021 Jan 21;20:160-173. doi: 10.17179/excli2020-2900. eCollection 2021.
9
MicroRNA-155-5p promotes hepatocellular carcinoma progression by suppressing PTEN through the PI3K/Akt pathway.微小RNA-155-5p通过PI3K/Akt信号通路抑制PTEN从而促进肝细胞癌进展。
Cancer Sci. 2017 Apr;108(4):620-631. doi: 10.1111/cas.13177. Epub 2017 Apr 19.
10
miR-455-5p enhances 5-fluorouracil sensitivity in colorectal cancer cells by targeting PIK3R1 and DEPDC1.微小RNA-455-5p通过靶向磷脂酰肌醇-3激酶调节亚基1（PIK3R1）和DEP结构域蛋白1（DEPDC1）增强结肠癌细胞对5-氟尿嘧啶的敏感性。
Open Med (Wars). 2022 Apr 28;17(1):847-856. doi: 10.1515/med-2022-0474. eCollection 2022.

引用本文的文献

1
Deciphering the roles of non-coding RNAs in liposarcoma development: Challenges and opportunities for translational therapeutic advances.解读非编码RNA在脂肪肉瘤发生发展中的作用：转化治疗进展面临的挑战与机遇
Noncoding RNA Res. 2024 Nov 15;11:73-90. doi: 10.1016/j.ncrna.2024.11.005. eCollection 2025 Apr.
2
Abnormal methylation mediated upregulation of LINC00857 boosts malignant progression of lung adenocarcinoma by modulating the miR-486-5p/NEK2 axis.异常甲基化介导的 LINC00857 上调通过调节 miR-486-5p/NEK2 轴促进肺腺癌的恶性进展。
Clin Respir J. 2024 May;18(5):e13765. doi: 10.1111/crj.13765.
3
Bioinformatics analysis of the potentially functional circRNA-miRNA-mRNA network in breast cancer.

本文引用的文献

1
ROCK2 Confers Acquired Gemcitabine Resistance in Pancreatic Cancer Cells by Upregulating Transcription Factor ZEB1.ROCK2通过上调转录因子ZEB1赋予胰腺癌细胞获得性吉西他滨耐药性。
Cancers (Basel). 2019 Nov 27;11(12):1881. doi: 10.3390/cancers11121881.
2
Down-regulation of miR-30a-5p is Associated with Poor Prognosis and Promotes Chemoresistance of Gemcitabine in Pancreatic Ductal Adenocarcinoma.miR-30a-5p的下调与胰腺导管腺癌的不良预后相关，并促进吉西他滨的化疗耐药性。
J Cancer. 2019 Aug 28;10(21):5031-5040. doi: 10.7150/jca.31191. eCollection 2019.
3
Long non-coding RNA PXN-AS1 suppresses pancreatic cancer progression by acting as a competing endogenous RNA of miR-3064 to upregulate PIP4K2B expression.
乳腺癌中潜在功能 circRNA-miRNA-mRNA 网络的生物信息学分析。
PLoS One. 2024 Apr 18;19(4):e0301995. doi: 10.1371/journal.pone.0301995. eCollection 2024.
4
In Vitro Antioxidant and Pancreatic Anticancer Activity of Novel 5-Fluorouracil-Coumarin Conjugates.新型5-氟尿嘧啶-香豆素缀合物的体外抗氧化和胰腺抗癌活性
Pharmaceutics. 2022 Oct 10;14(10):2152. doi: 10.3390/pharmaceutics14102152.
5
Biomarkers for early detection of pancreatic cancer - miRNAs as a potential diagnostic and therapeutic tool?用于胰腺癌早期检测的生物标志物——miRNA 作为一种有潜力的诊断和治疗工具？
Cancer Biol Ther. 2021 Jun 3;22(5-6):347-356. doi: 10.1080/15384047.2021.1941584. Epub 2021 Jul 5.
6
Overexpression of microRNA‑486 affects the proliferation and chemosensitivity of mesothelioma cell lines by targeting .miR-486 的过表达通过靶向. 影响间皮瘤细胞系的增殖和化疗敏感性。
Int J Mol Med. 2021 Jun;47(6). doi: 10.3892/ijmm.2021.4950. Epub 2021 May 6.
7
5-Fluorouracil: A Narrative Review on the Role of Regulatory Mechanisms in Driving Resistance to This Chemotherapeutic Agent.5-氟尿嘧啶：关于调节机制在导致对这种化疗药物产生耐药性中所起作用的叙述性综述
Front Oncol. 2021 Apr 19;11:658636. doi: 10.3389/fonc.2021.658636. eCollection 2021.
8
MiR-145 Regulates the Chemoresistance of Hepatic Carcinoma Cells Against 5-Fluorouracil by Targeting Toll-Like Receptor 4.微小RNA-145通过靶向Toll样受体4调控肝癌细胞对5-氟尿嘧啶的化疗耐药性
Cancer Manag Res. 2020 Jul 22;12:6165-6175. doi: 10.2147/CMAR.S257598. eCollection 2020.
长链非编码 RNA PXN-AS1 通过作为 miR-3064 的竞争性内源性 RNA 发挥作用，上调 PIP4K2B 表达，从而抑制胰腺癌的进展。
J Exp Clin Cancer Res. 2019 Sep 5;38(1):390. doi: 10.1186/s13046-019-1379-5.
4
Analysis of circulating cell-free DNA identifies KRAS copy number gain and mutation as a novel prognostic marker in Pancreatic cancer.循环无细胞 DNA 分析鉴定 KRAS 拷贝数增益和突变作为胰腺癌的一种新的预后标志物。
Sci Rep. 2019 Aug 12;9(1):11610. doi: 10.1038/s41598-019-47489-7.
5
MiR-486-5p Serves as a Good Biomarker in Nonsmall Cell Lung Cancer and Suppresses Cell Growth With the Involvement of a Target PIK3R1.MiR-486-5p作为非小细胞肺癌的良好生物标志物，并通过靶标PIK3R1抑制细胞生长。
Front Genet. 2019 Jul 26;10:688. doi: 10.3389/fgene.2019.00688. eCollection 2019.
6
Flavonoid Derivative of Demonstrates Therapeutic Potential in Preclinical Models of Metastatic Pancreatic Cancer.类黄酮衍生物在转移性胰腺癌临床前模型中显示出治疗潜力。
Front Oncol. 2019 Jul 23;9:660. doi: 10.3389/fonc.2019.00660. eCollection 2019.
7
MiR-205 mediated APC regulation contributes to pancreatic cancer cell proliferation.miR-205 介导的 APC 调控促进胰腺癌细胞增殖。
World J Gastroenterol. 2019 Jul 28;25(28):3775-3786. doi: 10.3748/wjg.v25.i28.3775.
8
miR-424-5p represses the metastasis and invasion of intrahepatic cholangiocarcinoma by targeting ARK5.miR-424-5p 通过靶向 ARK5 抑制肝内胆管癌的转移和侵袭。
Int J Biol Sci. 2019 Jun 4;15(8):1591-1599. doi: 10.7150/ijbs.34113. eCollection 2019.
9
Macrophage-derived exosomal microRNA-501-3p promotes progression of pancreatic ductal adenocarcinoma through the TGFBR3-mediated TGF-β signaling pathway.巨噬细胞衍生的外泌体 microRNA-501-3p 通过 TGFBR3 介导的 TGF-β 信号通路促进胰腺导管腺癌的进展。
J Exp Clin Cancer Res. 2019 Jul 15;38(1):310. doi: 10.1186/s13046-019-1313-x.
10
miR-486 Promotes Capan-2 Pancreatic Cancer Cell Proliferation by Targeting Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN).微小RNA-486通过靶向10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）促进卡潘-2胰腺癌细胞增殖。
Front Genet. 2019 Jun 14;10:541. doi: 10.3389/fgene.2019.00541. eCollection 2019.