MAGEA1通过激活Wnt/β-catenin信号通路促进恶性黑色素瘤的转移

许媛媛; 王晨; 贺赞; 王冬; 杨琼; 李永君; 郝永红; 胡辉莹; 方向东; 赵华

doi:10.3969/j.issn.2095-5227.2021.02.012

MAGEA1通过激活Wnt/β-catenin信号通路促进恶性黑色素瘤的转移

MAGEA1 promotes the metastasis of malignant melanoma by activating Wnt/β-catenin signaling pathway

摘要

摘要:
背景恶性黑色素瘤是源自黑色素细胞的恶性肿瘤，恶性程度高。其中转移性黑色素瘤患者的5年生存率不足10%，且发病率逐渐增加。黑色素瘤相关抗原家族A1(melanoma associated antigen family A1，MAGEA1)是MAGE-A基因亚家族的成员，在多种恶性肿瘤中均有表达，但其在恶性黑色素瘤中的表达和作用机制尚不明确。
目的探讨MAGEA1促进恶性黑色素瘤转移的信号通路，并进行验证。
方法通过黑色素瘤细胞系A375与A2058的RNA-Seq数据分析，确定MAGEA1正向调控Wnt/β-catenin信号通路，利用TOP/FOP、免疫荧光染色研究通路活性，利用Western blot和qRT-PCR分别在蛋白水平与转录水平验证通路基因的表达情况。
结果 MAGEA1通过c-Jun激活Wnt/β-catenin信号通路，促进黑色素瘤细胞上皮-间充质转化，提高黑色素瘤细胞的侵袭与迁移能力。
结论 MAGEA1作为一种与恶性肿瘤转移相关的基因，在恶性黑色素瘤中可通过激活Wnt/β-catenin信号通路促进细胞的转移。

Abstract:
Background Malignant melanoma is a malignant tumor derived from melanocytes. It is a life-threatening skin tumor. The five-year survival rate of patients with metastatic melanoma is less than 10%. Melanoma-associated antigen family A1 (MAGEA1) is a member of the MAGE-A gene subfamily, expressed in a variety of malignant tumors, but its intrinsic biological mechanism in malignant melanoma is still unclear.
Objective To explore the signal pathway of MAGEA1 in promoting the metastasis of malignant melanoma by activating Wnt/β-catenin signaling pathway, and verify it.
Methods The RNA-Seq data of melanoma cell lines A375 and A2058 were analyzed to determine the positive regulation of Wnt/β-catenin signal pathway by MAGEA1. The activity of the pathway was determined by TOP/FOP and immunofluorescence staining. Western blot and qRT-PCR were used to detection the gene expression of the pathway at protein level and transcriptional level, respectively.
Results MAGEA1 activated Wnt/β-catenin signal pathway through c-Jun, promoted the epithelial-mesenchymal transformation of melanoma cells, and aggravated the invasion and migration ability of melanoma cells.
Conclusion As a gene related to malignant tumor metastasis, MAGEA1 can promote cell metastasis by activating Wnt/β-catenin signal pathway in malignant melanoma.

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