m6A-Dependent ITIH1 Regulated by TGF-ß Acts as a Target for Hepatocellular Carcinoma Progression.
Adv Sci (Weinh)
; : e2401013, 2024 Sep 05.
Article
in En
| MEDLINE
| ID: mdl-39234824
ABSTRACT
Both the transforming growth factor beta (TGF-ß) signaling pathway and N6-methyladenosine (m6A) modification for mRNA play an important role in hepatocellular carcinoma (HCC) progression. However, the relationship between TGF-ß and m6A in hepatocellular carcinoma (HCC) remains unclear. Here, it is found that TGF-ß can promote the liquid phase separation of METTL3, which further leads to the reduction of mRNA stability of ITIH1. As a secreted protein, ITIH1 can act as a ligand of integrin α5ß1 to antagonize fibronectin, induce the inhibition of focal adhesion kinase signaling pathway, and inhibit the progression of HCC. In the preclinical model (mouse model, patient-derived organoid, patient-derived xenografts), purified recombinant ITIH1 (r-ITIH1) protein can be targeted for HCC. More importantly, r-ITIH1 can play a synergistic role in targeting HCC with TGF-ß inhibitor. The downstream ITIH1 regulatory mechanism of TGF-ß and m6A modification is revealed, and ITIH1 can be translational as a potential target for HCC.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Adv Sci (Weinh)
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: