Promoter hypermethylation-induced downregulation of ITGA7 promotes colorectal cancer proliferation and migration by activating the PI3K/AKT/NF-κB pathway.
Biochim Biophys Acta Mol Cell Res
; 1871(7): 119785, 2024 Oct.
Article
in En
| MEDLINE
| ID: mdl-38885843
ABSTRACT
We previously reported that integrin alpha 7 (ITGA7) was downregulated in colorectal cancer (CRC) tissues and CRC cell lines and that the lower expression of ITGA7 in CRC tissues was correlated with distant metastasis, suggesting that ITGA7 may function as a suppressor in CRC. The present research was conducted to further investigate the role and mechanisms of ITGA7 in CRC progression. First, bisulfite modification and genomic sequencing (BSP) results showed that the methylation rate of ITGA7 promoter was higher in 10 CRC tissues than in the matched normal tissues. Additionally, 5-Aza-CdR treatment increased ITGA7 expression in CRC cells. Gain-of-function assays revealed the inhibitory role of ITGA7 in CRC cell proliferation and migration. Mechanistically, RNA sequencing, RT-qPCR, and cytoplasm and nuclear separation and rescue assays indicated that knockdown of ITGA7 activated the transcription of MMP9, SETD7, and ADAM15 by enhancing the nuclear translocation of NF-κB. Moreover, CoIP and Western blot suggested a mechanistic model in which ITGA7 binds to CKAP4 to block the interaction of CKAP4 and PI3K p85α and thereby suppress the PI3K/AKT/NF-κB pathway. Accordingly, the current study suggests that ITGA7 functions as a suppressor in CRC progression and that its expression is controlled by promoter methylation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Signal Transduction
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Down-Regulation
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Gene Expression Regulation, Neoplastic
/
Cell Movement
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NF-kappa B
/
Promoter Regions, Genetic
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DNA Methylation
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Phosphatidylinositol 3-Kinases
/
Integrin alpha Chains
Limits:
Humans
Language:
En
Journal:
Biochim Biophys Acta Mol Cell Res
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Netherlands