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 : 2025-03-10 DOI:10.1007/s13258-025-01629-8

Chanhee Jung, Jieun Park, Sang Beom Seo

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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.

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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.