N-linked α2,6-sialylation of integrin β1 by the sialyltransferase ST6Gal1 promotes cell proliferation and stemness in gestational trophoblastic disease
- Placenta. 2024 Apr:149:18-28. doi: 10.1016/j.placenta.2024.03.004.
- 1. Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, China.
- 2. College of Life Science, Northeast Forestry University, Harbin, China; Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
- 3. Department of Pathology, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
- 4. The Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- 5. Department of Neurology and Psychiatry, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
- 6. Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. Electronic address: [email protected].
- 7. Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China. Electronic address: [email protected].
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. β-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 β1 and its significance in the activation of Integrin β1/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 β1 was highly α2,6-sialylated in JAR cells. Inhibition of ST6Gal1 reduced α2,6-sialylation on Integrin β1 and suppressed the Integrin β1/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 β1 signaling pathway in GTD. Therefore, ST6Gal1 may have a potential role in the occurrence and development of GTD.