The DEAD-box RNA helicase DDX5 (p68) and β-catenin: The crucial regulators of FOXM1 gene expression in arbitrating colorectal cancer.
Colorectal cancer
DEAD-box RNA helicase DDX5
FOXM1
Gene expression
TCF4
Thiostrepton
Wnt/β-catenin signaling
p68
β-Catenin
Journal
Biochimica et biophysica acta. Gene regulatory mechanisms
ISSN: 1876-4320
Titre abrégé: Biochim Biophys Acta Gene Regul Mech
Pays: Netherlands
ID NLM: 101731723
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
07
11
2022
revised:
23
02
2023
accepted:
22
03
2023
medline:
30
5
2023
pubmed:
31
3
2023
entrez:
30
3
2023
Statut:
ppublish
Résumé
Forkhead box M1 (FOXM1), a vital member of the Forkhead box family of transcription factors, helps in mediating oncogenesis. However, limited knowledge exists regarding the mechanistic insights into the FOXM1 gene regulation. DDX5 (p68), an archetypal member of the DEAD-box family of RNA helicases, shows multifaceted action in cancer progression by arbitrating RNA metabolism and transcriptionally coactivating transcription factors. Here, we report a novel mechanism of alliance between DDX5 (p68) and the Wnt/β-catenin pathway in regulating FOXM1 gene expression and driving colon carcinogenesis. Initial bioinformatic analyses highlighted elevated expression levels of FOXM1 and DDX5 (p68) in colorectal cancer datasets. Immunohistochemical assays confirmed that FOXM1 showed a positive correlation with DDX5 (p68) and β-catenin in both normal and colon carcinoma patient samples. Overexpression of DDX5 (p68) and β-catenin increased the protein and mRNA expression profiles of FOXM1, and the converse correlation occurred during downregulation. Mechanistically, overexpression and knockdown of DDX5 (p68) and β-catenin elevated and diminished FOXM1 promoter activity respectively. Additionally, Chromatin immunoprecipitation assay demonstrated the occupancy of DDX5 (p68) and β-catenin at the TCF4/LEF binding element (TBE) sites on the FOXM1 promoter. Thiostrepton delineated the effect of FOXM1 inhibition on cell proliferation and migration. Colony formation assay, migration assay, and cell cycle data reveal the importance of the DDX5 (p68)/β-catenin/FOXM1 axis in oncogenesis. Collectively, our study mechanistically highlights the regulation of FOXM1 gene expression by DDX5 (p68) and β-catenin in colorectal cancer.
Identifiants
pubmed: 36997114
pii: S1874-9399(23)00028-7
doi: 10.1016/j.bbagrm.2023.194933
pii:
doi:
Substances chimiques
beta Catenin
0
Ddx5 protein, human
EC 3.6.1.-
DEAD-box RNA Helicases
EC 3.6.4.13
Forkhead Box Protein M1
0
FOXM1 protein, human
0
Transcription Factors
0
CTNNB1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
194933Informations de copyright
Copyright © 2023. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no competing interests.