Silencing of CerS6 increases the invasion and glycolysis of melanoma WM35, WM451 and SK28 cell lines via increased GLUT1-induced downregulation of WNT5A
Silencing of CerS6 increases the invasion and glycolysis of melanoma WM35, WM451 and SK28 cell lines via increased GLUT1-induced downregulation of WNT5A
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CerS6 沉默通过增加 GLUT1 诱导的 WNT5A 下调来增加黑色素瘤 WM35、WM451 和 SK28 细胞系的侵袭和糖酵解
DOI：
10.3892/or.2016.4646
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发表时间：
2016-05-01
期刊：
影响因子：
4.2
通讯作者：
Xie, Huiqing
中科院分区：
文献类型：
--
作者：
Tang, Yuanyuan;Cao, Ke;Xie, Huiqing
神经酰胺脱氢酶（CerSs）已被证明调节癌症发展的许多方面。CerS 6被认为与癌症病因有关。然而，很少有人知道CerS 6对黑色素瘤的恶性行为，包括糖酵解，增殖和侵袭的确切影响。本研究发现CerS 6在WM 35、WM 451和SK-28等黑色素瘤细胞系中表达较低，且表达水平与黑色素瘤细胞系的恶性行为有关。我们构建了CerS 6在三种黑色素瘤细胞系中的过表达和沉默模型，发现CerS 6的沉默促进了黑色素瘤细胞系的增殖和侵袭能力。此外，CerS 6的下调上调糖酵解相关酶的活性，并增强糖酵解相关基因的表达，包括GLUT 1和MCT 1。此外，我们还通过基因芯片鉴定了CerS 6沉默后表达水平发生变化的基因。糖酵解相关基因SLC 2A 1（也称为GLUT 1）的表达被发现上调，而WNT 5A的表达显著下调。通过qPCR和蛋白质印迹验证GLUT 1和WNT 5A的表达改变。GLUT 1基因的沉默可导致WNT 5A基因表达的增加，从而降低黑色素瘤细胞的侵袭和增殖能力。总的来说，CerS 6的沉默诱导GLUT 1的表达增加，GLUT 1下调WNT 5A的表达，并增强黑色素瘤细胞的侵袭和增殖。因此，CerS 6可能为黑色素瘤治疗提供新的治疗靶点。
Ceramide synthases (CerSs) have been shown to regulate numerous aspects of cancer development. CerS6 has been suggested to be involved in cancer etiology. However, little is known concerning the exact effect of CerS6 on the malignant behavior of melanoma, including glycolysis, proliferation and invasion. In the present study, we found that the expression of CerS6 was low in the melanoma cell lines, including WM35, WM451 and SK-28, and the expression level was related to the malignanct behavior of the melanoma cell lines. We constructed overexpression and silencing models of CerS6 in three melanoma cell lines and found that silencing of CerS6 promoted the ability of proliferation and invasion in the melanoma cell lines. Additionally, downregulation of CerS6 upregulated the activity of glycolysis-related enzyme, and enhanced the expression of glycolysis-related genes, including GLUT1 and MCT1. Furthermore, we identified the genes whose expression levels were changed after silencing of CerS6 by gene microarray. The expression of glycolysis-related gene SLC2A1 (also known as GLUT1) was found to be upregulated, while notably WNT5A was downregulated. The altered expression of GLUT1 and WNT5A was verified by qPCR and western blotting. Furthermore, silencing of GLUT1 in the melanoma cells resulted in the increased expression of WNT5A and the decreased ability of invasion and proliferation in the melanoma cells. Collectively, silencing of CerS6 induced the increased expression of GLUT1, which downregulated the expression of WNT5A and enhanced the invasion and proliferation of melanoma cells. Thus, CerS6 may provide a novel therapeutic target for melanoma treatment.