In vivo CRISPR screen identifies LTN1 as a novel tumor suppressor ubiquitinating insulin-like growth factor 2 mRNA-binding protein 1 in hepatocellular carcinoma.
Hepatol Commun
; 7(10)2023 10 01.
Article
em En
| MEDLINE
| ID: mdl-37708447
ABSTRACT
BACKGROUND AND AIMS:
Hepatocellular carcinoma (HCC) is a frequent and aggressive kind of cancer. Although E3 ligases play important roles in HCC development, several E3 ligases remain unknown. APPROACH ANDRESULTS:
Through in vivo CRISPR knockout (KO) screens targeting related E3 ligase genes in HCC nude mice models, we discovered LTN1 as a novel tumor suppressor in HCC. Co-IP paired with 2D-LC-MS/MS and subsequent western blotting in HCC cells were used to identify the interactome of LTN1. Compared to matched normal tissues, the expression of LTN1 was decreased in human HCC tissues (ANT) (157/209). Clinically, patients with HCC who expressed low levels of LTN1 had a poor prognosis. Forced expression of LTN1 decreased cell growth in vitro and in vivo, whereas knockdown of LTN1 increased cell growth. Mechanistically, elevated LTN1 expression inhibited HCC cell growth by ubiquitinating and destabilizing the IGF2BP1 protein, which inhibited the c-Myc and IGF-1R signaling pathways. There was a negative correlation between the LTN1 protein expression and the IGF2BP1 protein expression in HCC tissues (R2=0.2799, P=0.0165).CONCLUSIONS:
LTN1 may be a crucial tumor suppressor for determining the prognosis and a possible therapeutic target since it inhibits the proliferation of HCC cells by ubiquitinating IGF2BP1.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Somatomedinas
/
Carcinoma Hepatocelular
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Neoplasias Hepáticas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article