Mechanisms of JAK-STAT signaling pathway mediated by CXCL8 gene silencing on epithelial-mesenchymal transition of human cutaneous melanoma cells.

Abstract

Effect of CXCL8 gene silencing-mediated JAK-STAT signaling pathway on epithelial-mesenchymal transition (EMT) of human cutaneous melanoma cells was explored. Eighty patients with cutaneous melanoma were enrolled in the study. Cells were transfected accordingly and divided into five groups: The blank group (human cutaneous melanoma cells), NC group (human cutaneous melanoma cells + blank vector plasmid transfection), CXCL8 siRNA group (human cutaneous melanoma cells + CXCL8 silent expression vector plasmid transfection), AG490 group (human cutaneous melanoma cells + JAK-STAT signal pathway inhibitor transfection), CXCL8 siRNA + AG490 group (human cutaneous melanoma cells + JAK-STAT signaling pathway inhibitor + CXCL8 silent expression vector plasmid transfection). The expression levels of CXCL8, JAK2, STAT3, epithelial cadherin (E-cadherin), neurotrophic cadherin (N-cadherin) and vimentin in tissues and cells were detected by RT-qPCR and western blot analysis. CCK-8 and flow cytometry were used to detect cell proliferation and apoptosis. Compared with adjacent normal tissues, the expression of E-cadherin in human cutaneous melanoma tissues was significantly decreased, whereas the expression of CXCL8, JAK2, STAT3, vimentin and N-cadherin was significantly increased (P<0.05). Compared with the blank group, CXCL8 siRNA group and CXCL8 siRNA + AG490 group had significantly lower expression of CXCL8 (P<0.05). Compared with the blank group, the expression levels of JAK2, STAT3, vimentin and N-cadherin in CXCL8 siRNA group, AG490 group and CXCL8 siRNA + AG490 group were decreased, the expression of E-cadherin was increased, the cell proliferation ability was decreased and apoptosis was increased (P<0.05). Compared with CXCL8 siRNA group, the expression of JAK2, STAT3, vimentin and N-cadherin in CXCL8 siRNA + AG490 group were significantly decreased, the expression of E-cadherin was significantly increased, cell proliferation ability was decreased and apoptosis was increased (P<0.05). In conclusion, CXCL8 gene expression silencing may inhibit EMT and cell proliferation while promoting cell apoptosis of human cutaneous melanoma cells by inhibiting the activation of JAK-STAT signaling pathway.