IDH1 突变会产生 R-2-hydroxyglutarate (R-2HG),并诱导 mir-182-5p 的表达,从而调节胶质瘤的细胞周期和肿瘤形成。

IF 4.3 2区 生物学 Q1 BIOLOGY
Haiting Zhao, Li Meng, Peng Du, Xinbin Liao, Xin Mo, Mengqi Gong, Jiaxin Chen, Yiwei Liao
{"title":"IDH1 突变会产生 R-2-hydroxyglutarate (R-2HG),并诱导 mir-182-5p 的表达,从而调节胶质瘤的细胞周期和肿瘤形成。","authors":"Haiting Zhao, Li Meng, Peng Du, Xinbin Liao, Xin Mo, Mengqi Gong, Jiaxin Chen, Yiwei Liao","doi":"10.1186/s40659-024-00512-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), are present in most gliomas. IDH1 mutation is an important prognostic marker in glioma. However, its regulatory mechanism in glioma remains incompletely understood.</p><p><strong>Results: </strong>miR-182-5p expression was increased within IDH1-mutant glioma specimens according to TCGA, CGGA, and online dataset GSE119740, as well as collected clinical samples. (R)-2-hydroxyglutarate ((R)-2HG) treatment up-regulated the expression of miR-182-5p, enhanced glioma cell proliferation, and suppressed apoptosis; miR-182-5p inhibition partially eliminated the oncogenic effects of R-2HG upon glioma cells. By direct binding to Cyclin Dependent Kinase Inhibitor 2 C (CDKN2C) 3'UTR, miR-182-5p inhibited CDKN2C expression. Regarding cellular functions, CDKN2C knockdown promoted R-2HG-treated glioma cell viability, suppressed apoptosis, and relieved cell cycle arrest. Furthermore, CDKN2C knockdown partially attenuated the effects of miR-182-5p inhibition on cell phenotypes. Moreover, CDKN2C knockdown exerted opposite effects on cell cycle check point and apoptosis markers to those of miR-182-5p inhibition; also, CDKN2C knockdown partially attenuated the functions of miR-182-5p inhibition in cell cycle check point and apoptosis markers. The engineered CS-NPs (antagomir-182-5p) effectively encapsulated and delivered antagomir-182-5p, enhancing anti-tumor efficacy in vivo, indicating the therapeutic potential of CS-NPs(antagomir-182-5p) in targeting the miR-182-5p/CDKN2C axis against R-2HG-driven oncogenesis in mice models.</p><p><strong>Conclusions: </strong>These insights highlight the potential of CS-NPs(antagomir-182-5p) to target the miR-182-5p/CDKN2C axis, offering a promising therapeutic avenue against R-2HG's oncogenic influence to glioma.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"30"},"PeriodicalIF":4.3000,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100189/pdf/","citationCount":"0","resultStr":"{\"title\":\"IDH1 mutation produces R-2-hydroxyglutarate (R-2HG) and induces mir-182-5p expression to regulate cell cycle and tumor formation in glioma.\",\"authors\":\"Haiting Zhao, Li Meng, Peng Du, Xinbin Liao, Xin Mo, Mengqi Gong, Jiaxin Chen, Yiwei Liao\",\"doi\":\"10.1186/s40659-024-00512-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), are present in most gliomas. IDH1 mutation is an important prognostic marker in glioma. However, its regulatory mechanism in glioma remains incompletely understood.</p><p><strong>Results: </strong>miR-182-5p expression was increased within IDH1-mutant glioma specimens according to TCGA, CGGA, and online dataset GSE119740, as well as collected clinical samples. (R)-2-hydroxyglutarate ((R)-2HG) treatment up-regulated the expression of miR-182-5p, enhanced glioma cell proliferation, and suppressed apoptosis; miR-182-5p inhibition partially eliminated the oncogenic effects of R-2HG upon glioma cells. By direct binding to Cyclin Dependent Kinase Inhibitor 2 C (CDKN2C) 3'UTR, miR-182-5p inhibited CDKN2C expression. Regarding cellular functions, CDKN2C knockdown promoted R-2HG-treated glioma cell viability, suppressed apoptosis, and relieved cell cycle arrest. Furthermore, CDKN2C knockdown partially attenuated the effects of miR-182-5p inhibition on cell phenotypes. Moreover, CDKN2C knockdown exerted opposite effects on cell cycle check point and apoptosis markers to those of miR-182-5p inhibition; also, CDKN2C knockdown partially attenuated the functions of miR-182-5p inhibition in cell cycle check point and apoptosis markers. The engineered CS-NPs (antagomir-182-5p) effectively encapsulated and delivered antagomir-182-5p, enhancing anti-tumor efficacy in vivo, indicating the therapeutic potential of CS-NPs(antagomir-182-5p) in targeting the miR-182-5p/CDKN2C axis against R-2HG-driven oncogenesis in mice models.</p><p><strong>Conclusions: </strong>These insights highlight the potential of CS-NPs(antagomir-182-5p) to target the miR-182-5p/CDKN2C axis, offering a promising therapeutic avenue against R-2HG's oncogenic influence to glioma.</p>\",\"PeriodicalId\":9084,\"journal\":{\"name\":\"Biological Research\",\"volume\":\"57 1\",\"pages\":\"30\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-05-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100189/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biological Research\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s40659-024-00512-2\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s40659-024-00512-2","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:大多数胶质瘤都存在异柠檬酸脱氢酶 1 和 2(IDH1 和 IDH2)突变。IDH1 突变是胶质瘤预后的重要标志。结果发现:根据 TCGA、CGGA 和在线数据集 GSE119740,以及收集的临床样本,IDH1 突变的胶质瘤标本中 miR-182-5p 表达增加。(R)-2-羟基戊二酸((R)-2HG)处理上调了 miR-182-5p 的表达,增强了胶质瘤细胞的增殖,抑制了细胞凋亡;抑制 miR-182-5p 可部分消除 R-2HG 对胶质瘤细胞的致癌作用。通过与细胞周期蛋白依赖性激酶抑制剂 2 C(CDKN2C)3'UTR 直接结合,miR-182-5p 抑制了 CDKN2C 的表达。在细胞功能方面,CDKN2C的敲除促进了R-2HG处理的胶质瘤细胞的活力,抑制了细胞凋亡,并缓解了细胞周期的停滞。此外,CDKN2C的敲除部分减弱了miR-182-5p抑制对细胞表型的影响。此外,CDKN2C敲除对细胞周期检查点和细胞凋亡标志物的影响与miR-182-5p抑制相反;CDKN2C敲除还部分削弱了miR-182-5p抑制对细胞周期检查点和细胞凋亡标志物的影响。工程化的CS-NPs(antagomir-182-5p)能有效封装和递送antagomir-182-5p,提高体内抗肿瘤疗效,表明CS-NPs(antagomir-182-5p)在靶向miR-182-5p/CDKN2C轴对抗R-2HG驱动的小鼠肿瘤发生方面具有治疗潜力:这些发现凸显了CS-NPs(antagomir-182-5p)靶向miR-182-5p/CDKN2C轴的潜力,为对抗R-2HG对胶质瘤的致癌影响提供了一条前景广阔的治疗途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
IDH1 mutation produces R-2-hydroxyglutarate (R-2HG) and induces mir-182-5p expression to regulate cell cycle and tumor formation in glioma.

Background: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), are present in most gliomas. IDH1 mutation is an important prognostic marker in glioma. However, its regulatory mechanism in glioma remains incompletely understood.

Results: miR-182-5p expression was increased within IDH1-mutant glioma specimens according to TCGA, CGGA, and online dataset GSE119740, as well as collected clinical samples. (R)-2-hydroxyglutarate ((R)-2HG) treatment up-regulated the expression of miR-182-5p, enhanced glioma cell proliferation, and suppressed apoptosis; miR-182-5p inhibition partially eliminated the oncogenic effects of R-2HG upon glioma cells. By direct binding to Cyclin Dependent Kinase Inhibitor 2 C (CDKN2C) 3'UTR, miR-182-5p inhibited CDKN2C expression. Regarding cellular functions, CDKN2C knockdown promoted R-2HG-treated glioma cell viability, suppressed apoptosis, and relieved cell cycle arrest. Furthermore, CDKN2C knockdown partially attenuated the effects of miR-182-5p inhibition on cell phenotypes. Moreover, CDKN2C knockdown exerted opposite effects on cell cycle check point and apoptosis markers to those of miR-182-5p inhibition; also, CDKN2C knockdown partially attenuated the functions of miR-182-5p inhibition in cell cycle check point and apoptosis markers. The engineered CS-NPs (antagomir-182-5p) effectively encapsulated and delivered antagomir-182-5p, enhancing anti-tumor efficacy in vivo, indicating the therapeutic potential of CS-NPs(antagomir-182-5p) in targeting the miR-182-5p/CDKN2C axis against R-2HG-driven oncogenesis in mice models.

Conclusions: These insights highlight the potential of CS-NPs(antagomir-182-5p) to target the miR-182-5p/CDKN2C axis, offering a promising therapeutic avenue against R-2HG's oncogenic influence to glioma.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Biological Research
Biological Research 生物-生物学
CiteScore
10.10
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: Biological Research is an open access, peer-reviewed journal that encompasses diverse fields of experimental biology, such as biochemistry, bioinformatics, biotechnology, cell biology, cancer, chemical biology, developmental biology, evolutionary biology, genetics, genomics, immunology, marine biology, microbiology, molecular biology, neuroscience, plant biology, physiology, stem cell research, structural biology and systems biology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信