• 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

激酶 GSK3β 通过 FTO 介导的 MZF1/c-Myc 轴在结直肠癌中作为抑制物发挥作用。

Kinase GSK3β functions as a suppressor in colorectal carcinoma through the FTO-mediated MZF1/c-Myc axis.

机构信息

Anorectal Department, Linyi People' s Hospital, Linyi, China.

出版信息

J Cell Mol Med. 2021 Mar;25(5):2655-2665. doi: 10.1111/jcmm.16291. Epub 2021 Feb 2.

DOI:10.1111/jcmm.16291
PMID:33533172
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7933972/
Abstract

Colorectal carcinoma (CRC) poses heavy burden to human health and has an increasing incidence. Currently, the existing biomarkers for CRC bring about restrained clinical benefits. GSK3β is reported to be a novel therapeutic target for this disease but with undefined molecular mechanisms. Thus, we aimed to investigate the regulatory effect of GSK3β on CRC progression via FTO/MZF1/c-Myc axis. Firstly, the expression patterns of GSK3β, FTO, MZF1 and c-Myc were determined after sample collection. Lowly expressed GSK3β but highly expressed FTO, MZF1 and c-Myc were found in CRC. After transfection of different overexpressed and interference plasmids, the underlying mechanisms concerning GSK3β in CRC cell functions were analysed. Additionally, the effect of GSK3β on FTO protein stability was assessed followed by detection of MZF1 m6A modification and MZF1-FTO interaction. Mechanistically, GSK3β mediated ubiquitination of demethylase FTO to reduce FTO expression. Besides, GSK3β inhibited MZF1 expression by mediating FTO-regulated m6A modification of MZF1 and then decreased the proto-oncogene c-Myc expression, thus hampering CRC cell proliferation. We also carried out in vivo experiment to verify the regulatory effect of GSK3β on CRC via FTO-mediated MZF1/c-Myc axis. It was found that GSK3β inhibited CRC growth in vivo which was reversed by overexpressing c-Myc. Taken together, our findings indicate that GSK3β suppresses the progression of CRC through FTO-regulated MZF1/c-Myc axis, shedding light onto a new possible pathway by which GSK3β regulates CRC.

摘要

结直肠癌（CRC）给人类健康带来了沉重负担，且其发病率呈上升趋势。目前，CRC 的现有生物标志物带来的临床获益有限。GSK3β 被报道为该疾病的一个新的治疗靶点，但分子机制尚未明确。因此，我们旨在通过 FTO/MZF1/c-Myc 轴研究 GSK3β 对 CRC 进展的调控作用。首先，在样本采集后确定了 GSK3β、FTO、MZF1 和 c-Myc 的表达模式。在 CRC 中发现 GSK3β 表达较低，而 FTO、MZF1 和 c-Myc 表达较高。转染不同的过表达和干扰质粒后，分析了 GSK3β 在 CRC 细胞功能中的潜在机制。此外，还评估了 GSK3β 对 FTO 蛋白稳定性的影响，随后检测了 MZF1 m6A 修饰和 MZF1-FTO 相互作用。从机制上讲，GSK3β 通过介导去甲基酶 FTO 的泛素化来降低 FTO 的表达。此外，GSK3β 通过调节 FTO 调控的 MZF1 m6A 修饰抑制 MZF1 的表达，进而降低原癌基因 c-Myc 的表达，从而抑制 CRC 细胞增殖。我们还进行了体内实验，通过 FTO 介导的 MZF1/c-Myc 轴验证了 GSK3β 对 CRC 的调节作用。结果发现，GSK3β 抑制了体内 CRC 的生长，而过表达 c-Myc 则逆转了这一作用。总之，我们的研究结果表明，GSK3β 通过 FTO 调节的 MZF1/c-Myc 轴抑制 CRC 的进展，为 GSK3β 调节 CRC 的新的可能途径提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/bf24d296c3ad/JCMM-25-2655-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/33d9d0a6619a/JCMM-25-2655-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/28ed9fb6a77e/JCMM-25-2655-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/1ab4a096d54d/JCMM-25-2655-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/b5eb4f7f1fa6/JCMM-25-2655-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/c8fd9443f69d/JCMM-25-2655-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/c364b01ec661/JCMM-25-2655-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/bf24d296c3ad/JCMM-25-2655-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/33d9d0a6619a/JCMM-25-2655-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/28ed9fb6a77e/JCMM-25-2655-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/1ab4a096d54d/JCMM-25-2655-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/b5eb4f7f1fa6/JCMM-25-2655-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/c8fd9443f69d/JCMM-25-2655-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/c364b01ec661/JCMM-25-2655-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab36/7933972/bf24d296c3ad/JCMM-25-2655-g007.jpg

相似文献

1
Kinase GSK3β functions as a suppressor in colorectal carcinoma through the FTO-mediated MZF1/c-Myc axis.激酶 GSK3β 通过 FTO 介导的 MZF1/c-Myc 轴在结直肠癌中作为抑制物发挥作用。
J Cell Mol Med. 2021 Mar;25(5):2655-2665. doi: 10.1111/jcmm.16291. Epub 2021 Feb 2.
2
microRNA-96 promotes occurrence and progression of colorectal cancer via regulation of the AMPKα2-FTO-m6A/MYC axis.microRNA-96 通过调控 AMPKα2-FTO-m6A/MYC 轴促进结直肠癌的发生发展。
J Exp Clin Cancer Res. 2020 Nov 12;39(1):240. doi: 10.1186/s13046-020-01731-7.
3
mA demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression.mA 去甲基酶 FTO 通过调节 MZF1 表达促进肺鳞癌肿瘤进展。
Biochem Biophys Res Commun. 2018 Aug 25;502(4):456-464. doi: 10.1016/j.bbrc.2018.05.175. Epub 2018 Jun 2.
4
Disruption of the c-Myc/miR-200b-3p/PRDX2 regulatory loop enhances tumor metastasis and chemotherapeutic resistance in colorectal cancer.破坏 c-Myc/miR-200b-3p/PRDX2 调控环路可增强结直肠癌的肿瘤转移和化疗耐药性。
J Transl Med. 2017 Dec 19;15(1):257. doi: 10.1186/s12967-017-1357-7.
5
HDAC3-dependent transcriptional repression of FOXA2 regulates FTO/m6A/MYC signaling to contribute to the development of gastric cancer.HDAC3 依赖性转录抑制因子 FOXA2 调节 FTO/m6A/MYC 信号通路促进胃癌的发生。
Cancer Gene Ther. 2021 Feb;28(1-2):141-155. doi: 10.1038/s41417-020-0193-8. Epub 2020 Jul 13.
6
RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3.RNA N6-甲基腺嘌呤去甲基化酶 FTO 通过抑制 BNIP3 促进乳腺癌进展。
Mol Cancer. 2019 Mar 28;18(1):46. doi: 10.1186/s12943-019-1004-4.
7
LncRNA FTO-IT1 promotes glycolysis and progression of hepatocellular carcinoma through modulating FTO-mediated N6-methyladenosine modification on GLUT1 and PKM2.长链非编码 RNA FTO-IT1 通过调节 FTO 介导的 GLUT1 和 PKM2 上的 N6-甲基腺苷修饰促进肝细胞癌的糖酵解和进展。
J Exp Clin Cancer Res. 2023 Oct 16;42(1):267. doi: 10.1186/s13046-023-02847-2.
8
Hypoxic Glioma Stem Cell-Derived Exosomes Containing Linc01060 Promote Progression of Glioma by Regulating the MZF1/c-Myc/HIF1α Axis.低氧胶质瘤干细胞来源的包含 linc01060 的外泌体通过调节 MZF1/c-Myc/HIF1α 轴促进胶质瘤的进展。
Cancer Res. 2021 Jan 1;81(1):114-128. doi: 10.1158/0008-5472.CAN-20-2270. Epub 2020 Nov 6.
9
Zinc finger protein 746 promotes colorectal cancer progression via c-Myc stability mediated by glycogen synthase kinase 3β and F-box and WD repeat domain-containing 7.锌指蛋白 746 通过糖原合酶激酶 3β 和 F-box 和 WD 重复结构域蛋白 7 介导的 c-Myc 稳定性促进结直肠癌的进展。
Oncogene. 2018 Jul;37(27):3715-3728. doi: 10.1038/s41388-018-0225-0. Epub 2018 Apr 9.
10
FTO downregulation mediated by hypoxia facilitates colorectal cancer metastasis.缺氧介导的FTO下调促进结直肠癌转移。
Oncogene. 2021 Aug;40(33):5168-5181. doi: 10.1038/s41388-021-01916-0. Epub 2021 Jul 3.

引用本文的文献

1
RNA Modifications in Health and Disease.健康与疾病中的RNA修饰
MedComm (2020). 2025 Sep 3;6(9):e70341. doi: 10.1002/mco2.70341. eCollection 2025 Sep.
2
Berbamine inhibits cell proliferation and invasion by increasing FTO expression in renal cell carcinoma cells.小檗胺通过增加肾癌细胞中FTO的表达来抑制细胞增殖和侵袭。
BMC Cancer. 2025 Jun 2;25(1):987. doi: 10.1186/s12885-025-13463-y.
3
Role and mechanisms of m6A demethylases in digestive system tumors.m6A去甲基化酶在消化系统肿瘤中的作用及机制

本文引用的文献

1
Expression Status And Prognostic Value Of M6A-associated Genes in Gastric Cancer.胃癌中m6A相关基因的表达状态及预后价值
J Cancer. 2020 Mar 4;11(10):3027-3040. doi: 10.7150/jca.40866. eCollection 2020.
2
Zinc Finger Transcription Factor MZF1-A Specific Regulator of Cancer Invasion.锌指转录因子 MZF1——癌症侵袭的特异性调控因子。
Cells. 2020 Jan 16;9(1):223. doi: 10.3390/cells9010223.
3
Colorectal cancer.结直肠癌。
Am J Cancer Res. 2025 Apr 15;15(4):1436-1460. doi: 10.62347/XMAF1290. eCollection 2025.
4
O-GlcNAcylated FTO promotes m6A modification of SOX4 to enhance MDS/AML cell proliferation.O-连接的N-乙酰葡糖胺化的FTO促进SOX4的m6A修饰以增强骨髓增生异常综合征/急性髓系白血病细胞增殖。
Cell Commun Signal. 2025 Jan 23;23(1):43. doi: 10.1186/s12964-025-02058-6.
5
Ramifications of m6A Modification on ncRNAs in Cancer.m6A修饰对癌症中非编码RNA的影响
Curr Genomics. 2024 May 31;25(3):158-170. doi: 10.2174/0113892029296712240405053201. Epub 2024 Apr 9.
6
Regulations of mA and other RNA modifications and their roles in cancer.mA 和其他 RNA 修饰的调控及其在癌症中的作用。
Front Med. 2024 Aug;18(4):622-648. doi: 10.1007/s11684-024-1064-8. Epub 2024 Jun 22.
7
Targeting RNA modifications with pharmacological agents: New frontiers in cancer therapy.靶向 RNA 修饰的药物治疗：癌症治疗的新前沿。
Cancer Med. 2024 Apr;13(7):e6989. doi: 10.1002/cam4.6989.
8
Ubiquitination and deubiquitination in the regulation of N-methyladenosine functional molecules.泛素化和去泛素化在 N6-甲基腺苷功能分子调控中的作用。
J Mol Med (Berl). 2024 Mar;102(3):337-351. doi: 10.1007/s00109-024-02417-9. Epub 2024 Jan 30.
9
The emerging role of mA modification of non-coding RNA in gastrointestinal cancers: a comprehensive review.非编码RNA的N6-甲基腺嘌呤修饰在胃肠道癌症中的新作用：综述
Front Cell Dev Biol. 2023 Oct 30;11:1264552. doi: 10.3389/fcell.2023.1264552. eCollection 2023.
10
Tumor cell-derived exosomes mediating hsa_circ_0001739/lncRNA AC159540.1 facilitate liver metastasis in colorectal cancer.肿瘤细胞来源的外泌体介导 hsa_circ_0001739/lncRNA AC159540.1 促进结直肠癌肝转移。
Cell Biol Toxicol. 2023 Dec;39(6):2551-2568. doi: 10.1007/s10565-023-09837-2. Epub 2023 Nov 14.
Lancet. 2019 Oct 19;394(10207):1467-1480. doi: 10.1016/S0140-6736(19)32319-0.
4
Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies.全球结直肠癌负担：趋势、风险因素和预防策略。
Nat Rev Gastroenterol Hepatol. 2019 Dec;16(12):713-732. doi: 10.1038/s41575-019-0189-8. Epub 2019 Aug 27.
5
Regulation of AKT phosphorylation by GSK3β and PTEN to control chemoresistance in breast cancer.通过 GSK3β 和 PTEN 调节 AKT 磷酸化以控制乳腺癌的化疗耐药性。
Breast Cancer Res Treat. 2019 Jul;176(2):291-301. doi: 10.1007/s10549-019-05239-3. Epub 2019 Apr 20.
6
FIBP knockdown attenuates growth and enhances chemotherapy in colorectal cancer via regulating GSK3β-related pathways.FIBP基因敲低通过调节与GSK3β相关的信号通路来抑制结直肠癌的生长并增强化疗效果。
Oncogenesis. 2018 Oct 2;7(9):77. doi: 10.1038/s41389-018-0088-9.
7
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.全球癌症统计数据 2018：GLOBOCAN 对全球 185 个国家/地区 36 种癌症的发病率和死亡率的估计。
CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
8
mA mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer.mA mRNA 甲基化调节 AKT 活性，促进子宫内膜癌的增殖和致瘤性。
Nat Cell Biol. 2018 Sep;20(9):1074-1083. doi: 10.1038/s41556-018-0174-4. Epub 2018 Aug 27.
9
mA demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression.mA 去甲基酶 FTO 通过调节 MZF1 表达促进肺鳞癌肿瘤进展。
Biochem Biophys Res Commun. 2018 Aug 25;502(4):456-464. doi: 10.1016/j.bbrc.2018.05.175. Epub 2018 Jun 2.
10
Glycogen synthase kinase-3 (GSK-3) activity regulates mRNA methylation in mouse embryonic stem cells.糖原合酶激酶-3（GSK-3）活性调节小鼠胚胎干细胞中的 mRNA 甲基化。
J Biol Chem. 2018 Jul 6;293(27):10731-10743. doi: 10.1074/jbc.RA117.001298. Epub 2018 May 18.