Article Abstract

Decreased Wnt4 expression inhibits thymoma development through downregulation of FoxN1

Authors: Yuan Chen, Xin Liu, Yimei Liu, Yuanguo Wang, Hai Wang, Chao Lu, Peng Zhang

Abstract

Background: The Wnt signaling pathway controls the development of thymic epithelial cells by regulating the expression of FoxN1. Thymoma is a type of malignant tumor arising from the thymic epithelial cells. To determine whether Wnt4 and FoxN1 are involved in the pathogenesis of thymoma, this study determined the mRNA and protein levels of Wnt4 and Foxn1 in thymoma, and analyzed the effect of thymoma cell apoptosis and tumor growth in nude mice after Wnt4 and FoxN1 downregulation.
Methods: Wnt4 and FoxN1 mRNA and protein levels in thymoma tissues were analyzed by RT-qPCR and immunohistochemistry, respectively. Thymoma cells were cultured and transfected with siRNA targeting the Wnt4, JNK, and FoxN1 genes. Apoptosis of thymoma cells were analyzed after Wnt4 and FoxN1 downregulation. In addition, thymoma cells were inoculated into nude mice and tumor growth was analyzed.
Results: The rates of expression of Wnt4 and FoxN1 protein were 64.3% and 58.9%, while the levels of mRNA expression were 2.56±0.04 and 1.83±0.11, respectively. With increasing malignancy of thymoma, the rates of positivity for Wnt4 and FoxN1 mRNA and protein expression gradually increased. Upon interfering with Wnt4, JNK, and FoxN1 gene expression by using siRNA technology, the inhibition rates were 56.7%, 72.6%, and 63.2%, respectively. The expression of FoxN1 mRNA and protein was decreased after Wnt4 and JNK downregulation. After downregulation of Wnt4 and FoxN1 gene expression, the apoptosis rate of thymoma cells increased and the tumor volume decreased in nude mice.
Conclusions: High expression of Wnt4 and FoxN1 may play an important role in the generation and development of thymoma. The FoxN1 gene produced a marked downstream effect through the regulation of Wnt4. Determining the positivity for both Wnt4 and FoxN1 can help us to evaluate the level of malignancy of thymoma.