E3 ligase MIB1 regulates STAT1/P21 signaling via regulation of FGFR1 in colorectal cancer.

IF 1.6 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & genomics Pub Date : 2025-06-01 Epub Date: 2025-03-10 DOI:10.1007/s13258-025-01629-8

Chanhee Jung, Jieun Park, Sang Beom Seo

{"title":"E3 ligase MIB1 regulates STAT1/P21 signaling via regulation of FGFR1 in colorectal cancer.","authors":"Chanhee Jung, Jieun Park, Sang Beom Seo","doi":"10.1007/s13258-025-01629-8","DOIUrl":null,"url":null,"abstract":"Background: Mind bomb 1 (MIB1) is an E3 ubiquitin ligase that promotes the polyubiquitination-mediated degradation of NOTCH ligands and plays an important role in various cancers by enhancing tumor cell proliferation. Also, MIB1 inhibited the cell cycle progression by transcriptional repression of P21 in HCT116 cells. Fibroblast growth factor receptor 1 (FGFR1) is a receptor tyrosine kinase (RTK) that plays a significant role in the progression of various cancers. However, the regulatory mechanisms underlying FGFR1-associated signaling in colon cancer remain unclear.Objective: We investigated whether MIB1 regulates protein stability of FGFR1 and impairs cell proliferation in HCT116 cells.Methods: We conducted immunoprecipitation assay to identify correlation of MIB1 and FGFR1. We also tested mRNA level of FGFR1 in MIB1-depleted HCT116 cells using reverse transcription-quantitative polymerase chain reaction. Furthermore, we transfected HA-MIB1 and FLAG-FGFR1 and analyzed the downstream signaling cascades by western blotting. Cell viability was assessed using colony formation assays and MTT assay.Results: FGFR1 interacts with MIB1 and controls FGFR1 protein level in HCT116 cells. Transcriptome analysis revealed that the mRNA levels of FGFR1 increased when MIB1 was depleted in HCT116 cells. Moreover, histone deacetylase 3 (HDAC3) is involved in histone deacetylation and transcriptional repression, mediating the interaction between MIB1 and FGFR1.Conclusion: These findings suggest the importance of MIB1-mediated transcriptional repression of FGFR1 and its potential therapeutic target in colon cancer.","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"663-670"},"PeriodicalIF":1.6000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genes & genomics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s13258-025-01629-8","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/10 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Mind bomb 1 (MIB1) is an E3 ubiquitin ligase that promotes the polyubiquitination-mediated degradation of NOTCH ligands and plays an important role in various cancers by enhancing tumor cell proliferation. Also, MIB1 inhibited the cell cycle progression by transcriptional repression of P21 in HCT116 cells. Fibroblast growth factor receptor 1 (FGFR1) is a receptor tyrosine kinase (RTK) that plays a significant role in the progression of various cancers. However, the regulatory mechanisms underlying FGFR1-associated signaling in colon cancer remain unclear.

Objective: We investigated whether MIB1 regulates protein stability of FGFR1 and impairs cell proliferation in HCT116 cells.

Methods: We conducted immunoprecipitation assay to identify correlation of MIB1 and FGFR1. We also tested mRNA level of FGFR1 in MIB1-depleted HCT116 cells using reverse transcription-quantitative polymerase chain reaction. Furthermore, we transfected HA-MIB1 and FLAG-FGFR1 and analyzed the downstream signaling cascades by western blotting. Cell viability was assessed using colony formation assays and MTT assay.

Results: FGFR1 interacts with MIB1 and controls FGFR1 protein level in HCT116 cells. Transcriptome analysis revealed that the mRNA levels of FGFR1 increased when MIB1 was depleted in HCT116 cells. Moreover, histone deacetylase 3 (HDAC3) is involved in histone deacetylation and transcriptional repression, mediating the interaction between MIB1 and FGFR1.

Conclusion: These findings suggest the importance of MIB1-mediated transcriptional repression of FGFR1 and its potential therapeutic target in colon cancer.

查看原文本刊更多论文

E3连接酶MIB1通过调节结直肠癌中的FGFR1调控STAT1/P21信号。

背景：脑炸弹1 （Mind bomb 1, MIB1）是一种E3泛素连接酶，可促进多泛素化介导的NOTCH配体降解，通过促进肿瘤细胞增殖在多种癌症中发挥重要作用。此外，在HCT116细胞中，MIB1通过转录抑制P21抑制细胞周期进程。成纤维细胞生长因子受体1 （FGFR1）是一种酪氨酸激酶受体（RTK），在各种癌症的进展中起重要作用。然而，结肠癌中fgfr1相关信号的调控机制仍不清楚。目的：研究MIB1是否调节HCT116细胞中FGFR1蛋白的稳定性并损害细胞增殖。方法：采用免疫沉淀法检测MIB1与FGFR1的相关性。我们还使用逆转录-定量聚合酶链反应检测了mib1缺失的HCT116细胞中FGFR1的mRNA水平。此外，我们转染了HA-MIB1和FLAG-FGFR1，并通过western blotting分析了下游信号级联。采用菌落形成法和MTT法测定细胞活力。结果：FGFR1与MIB1相互作用并控制HCT116细胞中FGFR1蛋白水平。转录组分析显示，当HCT116细胞中MIB1缺失时，FGFR1的mRNA水平升高。此外，组蛋白去乙酰化酶3 （HDAC3）参与组蛋白去乙酰化和转录抑制，介导MIB1和FGFR1之间的相互作用。结论：这些发现提示mib1介导的FGFR1转录抑制的重要性及其在结肠癌中的潜在治疗靶点。

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

Genes & genomics 生物-生化与分子生物学

CiteScore

3.70

自引率

4.80%

发文量

131

审稿时长

6-12 weeks

期刊介绍： Genes & Genomics is an official journal of the Korean Genetics Society (http://kgenetics.or.kr/). Although it is an official publication of the Genetics Society of Korea, membership of the Society is not required for contributors. It is a peer-reviewed international journal publishing print (ISSN 1976-9571) and online version (E-ISSN 2092-9293). It covers all disciplines of genetics and genomics from prokaryotes to eukaryotes from fundamental heredity to molecular aspects. The articles can be reviews, research articles, and short communications.