IRE1α-XBP1通过上调IL-6表达促进黑色素瘤细胞增殖的分子机制

Objective To investigate the role and molecular mechanism of IRE1α-XBP1 pathway in melanoma cell proliferation during endoplasmic reticulum stress. Methods Clinical information of 61 patients with melanoma from Zhongshan Hospital,Fudan University were obtained and analyzed.The melanoma specimens and corresponding normal tissues from patients were stained with XBP1.The mRNA level of XBP1s was detected in human tissues and cell lines.XBP1s and IL-6 expression levels were determined in both melanocytes (HEMn-MP) and melanoma cells (Mel-RMu) overexpressing the IRE1α or XBP1s.The cell proliferation was detected with or without IL-6 neutralizing antibody. Results The mRNA and protein expression levels of XBP1s were significantly elevated in human melanoma tissues and cell lines compared with normal tissues or melanocytes.Ectopic expression of IRE1α or XBP1s robustly enhanced IL-6 expression in HEMn-MP and Mel-RMu cells.Moreover,overexpression of IRE1α or XBP1s significantly promoted melanoma cells (Mel-RMu) proliferation which was blocked by IL-6 neutralizing antibody. Conclusions Our results reveal that the IRE1α-XBP1s-IL-6 pathway regulates melanoma cell proliferation by activating IL-6 section.