Aberrantly enhanced melanoma-associated antigen (MAGE)-A3 expression facilitates cervical cancer cell proliferation and metastasis via actuating Wnt signaling pathway.

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.