Title:Silencing FUT4 Inhibits the Progression of Osteosarcoma through Activation of
FOXO1
Volume: 30
Issue: 6
Author(s): Yang Yang, Xiaodi Yan, YueYuan Chen, Jiajia Liu, Jianhua Xue, Xiaoming Sheng, Jun Qin, Qiang Xue*Xianchen Liu*
Affiliation:
- Department
of Radiation Oncology, Affiliated Hospital of Nantong University, Nantong City, Jiangsu Province 226001, China
- Department
of Radiation Oncology, Affiliated Hospital of Nantong University, Nantong City, Jiangsu Province 226001, China
Keywords:
FOXO1, FUT4, osteosarcoma cells, proliferation, migration, apoptosis.
Abstract:
Background: It has been reported that inhibition of Fucosyltransferase4 (FUT4) to activate Forkhead
box O1 (FOXO1) can lead to apoptosis of cancer cells, however, the mechanism in osteosarcoma is still
unclear.
Objective: To explore the biological significance of the connection between FUT4 and FOXO1 in osteosarcoma
growth.
Methods: In vitro tests were conducted using the human osteoblast cell line and the osteosarcoma cell lines.
QRT-PCR assay as well as western blot assay were used to ascertain the relative expression levels of FUT4
and FOXO1 in the cells. By using the CCK-8 assay, colony assay, EDU assay, wound healing assay and Transwell
assay, osteosarcoma cells' ability to proliferate, migrate and invade were examined in relation to si-
FUT4. TUNEL test was used to evaluate Si-impact FUT4's on KHOS and U2OS apoptosis in osteosarcoma
cells. Western blot assay was used to identify the expression of proliferative, migrating and apoptosis-related
protein markers in osteosarcoma cells KHOS and U2OS and the expression of important proteins in the Wnt/
β-catenin signaling pathway.
Results: In comparison with osteoblasts, osteosarcoma cells expressed more FUT4. The osteosarcoma cells' capacities
to proliferate, invade, and migrate were markedly inhibited by the inhibition of FUT4 expression,
which also increased osteosarcoma cell apoptosis. The Wnt/β-catenin signaling pathway was blocked by upregulating
FOXO1 expression, which was in turn inhibited by inhibiting FUT4 expression.
Conclusion: Osteosarcoma cells express more FUT4. The Wnt/β-catenin signaling pathway has a significant
effect on osteosarcoma cell death, and inhibition of FUT4 expression may target FOXO1 activation to decrease
osteosarcoma cells' ability to proliferate, invade, and migrate.
