Exosomes containing circSCP2 in colorectal cancer promote metastasis via sponging miR-92a-1-5p and interacting with PTBP1 to stabilize IGF2BP1.

IF 5.7 2区 生物学 Q1 BIOLOGY
Qing Meng, Haoyi Xiang, Yijing Wang, Kepeng Hu, Xin Luo, Jiawei Wang, Engeng Chen, Wei Zhang, Jiaxin Chen, Xiaoyu Chen, Huogang Wang, Zhenyu Ju, Zhangfa Song
{"title":"Exosomes containing circSCP2 in colorectal cancer promote metastasis via sponging miR-92a-1-5p and interacting with PTBP1 to stabilize IGF2BP1.","authors":"Qing Meng, Haoyi Xiang, Yijing Wang, Kepeng Hu, Xin Luo, Jiawei Wang, Engeng Chen, Wei Zhang, Jiaxin Chen, Xiaoyu Chen, Huogang Wang, Zhenyu Ju, Zhangfa Song","doi":"10.1186/s13062-024-00571-1","DOIUrl":null,"url":null,"abstract":"<p><p>Exosomes have emerged as significant biomarkers for multiple diseases, including cancers. Circular RNAs (circRNAs), abundant in exosomes, are involved in regulating cancer development. However, the regulatory function and the underlying molecular mechanism of hsa_circ_0006906 (circSCP2) in colorectal cancer (CRC) metastasis remain unclear. A competing endogenous RNA microarray was used to analyze circRNA expression in serum exosomes in patients with CRC at early and late stages. circSCP2 expression was evaluated using qRT-PCR. The biological functions of circSCP2 in CRC were assessed through in vitro and in vivo experiments. The molecular mechanism of circSCP2 was explored using western blotting, RNA pulldown, RNA immunoprecipitation, luciferase assays, and relative rescue experiments. circSCP2 expression was significantly elevated in CRC tissues, with higher levels in serum exosomes correlating with advanced TNM stages. circSCP2 knockdown inhibited CRC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Mechanistically, circSCP2 sponged miR-92a-1-5p to increase insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) expression. Additionally, circSCP2 directly bound to and stabilized polypyrimidine tract binding protein 1 (PTBP1) by inhibiting protein ubiquitination, resulting in IGF2BP1 mRNA stabilization and enhanced CRC migration and invasion. Our findings demonstrate that circSCP2 regulates the miR-92a-1-5p/IGF2BP1 pathway, promotes PTBP1/IGF2BP1 interaction, and accelerates CRC progression. Exosomal circSCP2 is a promising circulating biomarker for CRC prognosis and needs further therapeutic investigation.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"130"},"PeriodicalIF":5.7000,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661319/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biology Direct","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13062-024-00571-1","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

Abstract

Exosomes have emerged as significant biomarkers for multiple diseases, including cancers. Circular RNAs (circRNAs), abundant in exosomes, are involved in regulating cancer development. However, the regulatory function and the underlying molecular mechanism of hsa_circ_0006906 (circSCP2) in colorectal cancer (CRC) metastasis remain unclear. A competing endogenous RNA microarray was used to analyze circRNA expression in serum exosomes in patients with CRC at early and late stages. circSCP2 expression was evaluated using qRT-PCR. The biological functions of circSCP2 in CRC were assessed through in vitro and in vivo experiments. The molecular mechanism of circSCP2 was explored using western blotting, RNA pulldown, RNA immunoprecipitation, luciferase assays, and relative rescue experiments. circSCP2 expression was significantly elevated in CRC tissues, with higher levels in serum exosomes correlating with advanced TNM stages. circSCP2 knockdown inhibited CRC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Mechanistically, circSCP2 sponged miR-92a-1-5p to increase insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) expression. Additionally, circSCP2 directly bound to and stabilized polypyrimidine tract binding protein 1 (PTBP1) by inhibiting protein ubiquitination, resulting in IGF2BP1 mRNA stabilization and enhanced CRC migration and invasion. Our findings demonstrate that circSCP2 regulates the miR-92a-1-5p/IGF2BP1 pathway, promotes PTBP1/IGF2BP1 interaction, and accelerates CRC progression. Exosomal circSCP2 is a promising circulating biomarker for CRC prognosis and needs further therapeutic investigation.

结直肠癌中含有circSCP2的外泌体通过海绵化miR-92a-1-5p和与PTBP1相互作用稳定IGF2BP1来促进转移。
外泌体已成为包括癌症在内的多种疾病的重要生物标志物。外泌体中丰富的环状rna (circRNAs)参与调节癌症的发展。然而,hsa_circ_0006906 (circSCP2)在结直肠癌(CRC)转移中的调控功能及其潜在的分子机制尚不清楚。使用竞争性内源性RNA微阵列分析早期和晚期结直肠癌患者血清外泌体中的circRNA表达。采用qRT-PCR检测circSCP2的表达。通过体外和体内实验评估circSCP2在结直肠癌中的生物学功能。通过western blotting、RNA拉下、RNA免疫沉淀、荧光素酶测定和相关抢救实验探讨circSCP2的分子机制。circSCP2在结直肠癌组织中的表达显著升高,血清外泌体中较高的表达水平与TNM晚期相关。circSCP2基因敲低可抑制CRC细胞的增殖、迁移、侵袭和转移。在机制上,circSCP2海绵miR-92a-1-5p增加胰岛素样生长因子2 mrna结合蛋白1 (IGF2BP1)的表达。此外,circSCP2通过抑制蛋白泛素化,直接结合并稳定聚嘧啶束结合蛋白1 (PTBP1),导致IGF2BP1 mRNA稳定,增强结直肠癌的迁移和侵袭。我们的研究结果表明,circSCP2调节miR-92a-1-5p/IGF2BP1通路,促进PTBP1/IGF2BP1相互作用,加速CRC进展。外泌体circSCP2是一种很有前景的CRC预后循环生物标志物,需要进一步的治疗研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Biology Direct
Biology Direct 生物-生物学
CiteScore
6.40
自引率
10.90%
发文量
32
审稿时长
7 months
期刊介绍: Biology Direct serves the life science research community as an open access, peer-reviewed online journal, providing authors and readers with an alternative to the traditional model of peer review. Biology Direct considers original research articles, hypotheses, comments, discovery notes and reviews in subject areas currently identified as those most conducive to the open review approach, primarily those with a significant non-experimental component.
×
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