Aberrantly enhanced melanoma-associated antigen (MAGE)-A3 expression facilitates cervical cancer cell proliferation and metastasis via actuating Wnt signaling pathway
Aberrantly enhanced melanoma-associated antigen (MAGE)-A3 expression facilitates cervical cancer cell proliferation and metastasis via actuating Wnt signaling pathway
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黑色素瘤相关抗原（MAGE）-A3表达异常增强，通过启动Wnt信号通路促进宫颈癌细胞增殖和转移
DOI：
10.1016/j.biopha.2019.109710
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发表时间：
2020-02-01
影响因子：
7.5
通讯作者：
He, Yuanli
中科院分区：
文献类型：
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作者：
Gao, Xinping;Chen, Guobin;He, Yuanli
背景：我们前期研究发现黑色素瘤相关抗原（melanoma-associated antigen， MAGE）-A3在宫颈癌（cervical cancer， CC）中过表达，提示其可能在CC的发生发展和转移过程中发挥重要作用，本研究旨在探讨MAGE-A3在CC发展过程中的生物学功能及其作用机制。方法：采用实时定量反转录PCR （real-time quantitative reverse transcription PCR, qRT-PCR）检测MAGE-A3 mRNA在End1/E6E7和CC细胞株HeLa、SiHa和C33A中的表达。采用功能丧失法和功能获得法评估MAGE-A3对HeLa和SiHa细胞增殖、迁移和侵袭能力的影响。Western blot检测上皮-间质转化（epithelial-mesenchymal transition， EMT）相关蛋白和Wnt信号通路蛋白的表达水平。采用体内肿瘤发生实验评价MAGE-A3对肿瘤生长的影响。结果：与End1/E6E7细胞系相比，MAGE-A3在CC细胞系（HeLa、SiHa和C33A）中的表达明显上调。下调MAGE-A3可显著抑制HeLa细胞的迁移、侵袭和增殖；而在SiHa细胞中过表达MAGE-A3则呈现相反的结果。此外，MAGE-A3的下调对HeLa细胞中EMT和Wnt信号通路的激活具有抑制作用，而上调MAGE-A3在SiHa细胞中表现出相反的结果。通过体内肿瘤发生实验，我们进一步验证了MAGE-A3在肿瘤生长中的促进作用。结论：MAGE-A3在CC细胞中过表达，可能通过调节EMT和Wnt信号通路促进CC细胞的活力和运动。本研究提示MAGE-A3可能是CC患者的潜在治疗靶点和预后预测因子。
Background: The over-expression of melanoma-associated antigen (MAGE)-A3 in cervical cancer (CC) has been observed in our previous study, suggesting that it possibly take a vital role during the development and metastasis of CC. The present study aimed to investigate the biological function of MAGE-A3 in the progression of CC and explore how it executes its roles.Methods: The mRNA expression of MAGE-A3 in End1/E6E7 and CC cell lines (HeLa, SiHa and C33A) was measured by real-time quantitative reverse transcription PCR (qRT-PCR). Loss- and gain-of-function methods were used to assess the effect of MAGE-A3 on the proliferative, migratory and invasive abilities of HeLa and SiHa cells. Western blot was performed to measure the expression levels of proteins related to epithelial-mesenchymal transition (EMT) and proteins in the Wnt signaling pathway. In vivo tumorigenesis assay was conducted to evaluate the effect of MAGE-A3 on tumor growth.Results: MAGE-A3 expression was significantly up-regulated in CC cell lines (HeLa, SiHa and C33A) compared with that in End1/E6E7 cell line. Knockdown of MAGE-A3 could significantly suppress migration, invasion and proliferation in HeLa cells; whereas, overexpression of MAGE-A3 in SiHa cells presented the opposite results. Moreover, knockdown of MAGE-A3 presented a suppressive effect on the activation of EMT and Wnt signaling pathway in HeLa cells, whilst up-regulation of MAGE-A3 exhibited the opponent outcomes in SiHa cells. Through in vivo tumorigenesis assay, we further verified that MAGE-A3 acted as a facilitator in tumor growth.Conclusions: MAGE-A3 is overexpressed in CC cells and possibly facilitates the viability and motility of CC cells via modulating EMT and Wnt signaling. This study implied that MAGE-A3 might be a potential therapeutic target as well as a prognosis predictor for patients with CC.