IGF2BP2 promotes ovarian cancer growth and metastasis by upregulating CKAP2L protein expression in an m6 A-dependent manner.
FASEB J
; 37(10): e23183, 2023 10.
Article
in En
| MEDLINE
| ID: mdl-37665628
ABSTRACT
Ovarian cancer (OC) is the second leading cause of gynecological cancer-related death in women worldwide. N6-methyladenosine (m6 A) is the most abundant internal modification in eukaryotic RNA. Human insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an m6 A reader, can enhance mRNA stability and promote translation by recognizing m6 A modifications. Its tumor-promoting effects have been demonstrated in several cancers. However, the roles of m6 A modification and IGF2BP2 in OC remain unclear. Here, by using methylated RNA immunoprecipitation sequencing, we demonstrated that there is widespread dysregulation of m6 A modification in OC tissues. The m6 A modification and the mRNA and protein levels of IGF2BP2 were significantly elevated in OC. Overexpression of IGF2BP2 facilitated OC cell proliferation, migration, and invasion in vitro and accelerated tumor growth and metastasis in vivo. While IGF2BP2-knockdown showed the opposite effect. Mechanistically, we identified cytoskeleton-associated protein 2-like (CKAP2L) as a target of IGF2BP2. IGF2BP2 promoted CKAP2L translation dependent on m6 A modification, rather than affecting mRNA and protein stability. Overexpression of CKAP2L rescued the tumor-suppressive effect of IGF2BP2 knockdown in OC cells. In conclusion, this study revealed the potential role of IGF2BP2 in tumor progression, at least partially via promoting the translation of CKAP2L in an m6 A-dependent manner.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
RNA-Binding Proteins
/
Cytoskeletal Proteins
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
Language:
En
Journal:
FASEB J
Journal subject:
BIOLOGIA
/
FISIOLOGIA
Year:
2023
Document type:
Article
Affiliation country:
China