It is critical to understand the risk factors responsible for the tumorigenesis and progression of nasopharyngeal carcinoma (NPC). Bisphenol A (BPA) can regulate the estrogenic signals to modulate cancer progression, while its roles in NC were not investigated. Our present study revealed that the BPA can increase proliferation and migration of NPC cells while decrease the chemosensitivity to doxorubicin (Dox). The inhibitor of GSK-3β/β-catenin (LiCl) can restore BPA-induced cell proliferation of NPC cells, which is due to that BPA can decrease phosphorylation while increase expression and nucleus localization of β-catenin. Mechanistically, BPA can increase the mRNA stability of β-catenin (encoded by CTNNB1) via suppressing the expression of miR-214-3p, which can direct target the 3'UTR of β-catenin mRNA. Further, BPA can decrease phosphorylation of β-catenin via repressing the expression of CK1α. Collectively, our data showed that BPA can trigger the proliferation and malignancy of NPC cells via activation of Wnt/β-catenin pathway. It indicated that body accumulation and inhalation exposure of BPA might be a risk factor for NPC development.

中文翻译：

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双酚A通过激活Wnt /β-catenin途径触发鼻咽癌细胞的恶性肿瘤。

了解导致鼻咽癌（NPC）发生和发展的危险因素至关重要。双酚A（BPA）可以调节雌激素信号来调节癌症进展，但尚未研究其在NC中的作用。我们目前的研究表明，双酚A可以增加NPC细胞的增殖和迁移，同时降低对阿霉素（Dox）的化学敏感性。GSK-3β/β-catenin（LiCl）的抑制剂可以恢复BPA诱导的NPC细胞增殖，这是由于BPA可以减少磷酸化，同时增加β-catenin的表达和细胞核定位。从机理上讲，BPA可以通过抑制miR-214-3p的表达来增强β-catenin的mRNA稳定性（由CTNNB1编码），而miR-214-3p可以直接靶向β-cateninmRNA的3'UTR。进一步，BPA可以通过抑制CK1α的表达来降低β-catenin的磷酸化。总体而言，我们的数据表明BPA可以通过激活Wnt /β-catenin途径来触发NPC细胞的增殖和恶性。这表明BPA的体内积累和吸入暴露可能是NPC发生的危险因素。