N-linked α2,6-sialylation of integrin ß1 by the sialyltransferase ST6Gal1 promotes cell proliferation and stemness in gestational trophoblastic disease.
Placenta
; 149: 18-28, 2024 04.
Article
in En
| MEDLINE
| ID: mdl-38490094
ABSTRACT
INTRODUCTION:
Gestational trophoblastic disease (GTD) encompasses a spectrum of rare pre-malignant and malignant entities originating from trophoblastic tissue, including partial hydatidiform mole, complete hydatidiform mole and choriocarcinoma. ß-galactoside α2,6 sialyltransferase 1 (ST6Gal1), the primary sialyltransferase responsible for the addition of α2,6 sialic acids, is strongly associated with the occurrence and development of several tumor types. However, the role of ST6Gal1/α2,6 -sialylation of trophoblast cells in GTD is still not well understood.METHODS:
The expression of ST6Gal1 was investigated in GTD and human immortalized trophoblastic HTR-8/SVneo cells and human gestational choriocarcinoma JAR cells. We evaluated the effect of ST6Gal1 on proliferation and stemness of trophoblastic cells. We also examined the effect of internal miR-199a-5p on ST6Gal1 expression. The role of ST6Gal1 in regulating α2,6-sialylated integrin ß1 and its significance in the activation of integrin ß1/focal adhesion kinase (FAK) signaling pathway were also explored.RESULTS:
ST6Gal1 was observed to be highly expressed in GTD. Overexpression of ST6Gal1 promoted the proliferation and stemness of HTR-8/SVneo cells, whereas knockdown of ST6Gal1 suppressed the viability and stemness of JAR cells. MiR-199a-5p targeted and inhibited the expression of ST6Gal1 in trophoblastic cells. In addition, we revealed integrin ß1 was highly α2,6-sialylated in JAR cells. Inhibition of ST6Gal1 reduced α2,6-sialylation on integrin ß1 and suppressed the integrin ß1/FAK pathway in JAR cells, thereby affecting its biological functions.DISCUSSION:
This study demonstrated that ST6Gal1 plays important roles in promoting proliferation and stemness through the integrin ß1 signaling pathway in GTD. Therefore, ST6Gal1 may have a potential role in the occurrence and development of GTD.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Choriocarcinoma
/
Integrin beta1
/
Gestational Trophoblastic Disease
/
MicroRNAs
Limits:
Female
/
Humans
/
Pregnancy
Language:
En
Journal:
Placenta
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Netherlands