Abstract：
Nasopharyngeal carcinoma (NPC) refers to a malignancy initiating from the superior mucosal epithelium of the nasopharynx. Optimal therapies for NPC are still needed. In this investigation, we attempted to explore whether BarH-like homeobox 2 (BARX2), a well-known tumor suppressor, had anti-cancer properties on NPC, and the possible mechanisms. After searching for NPC-related databases, we determined BARX2 as one of the core genes in NPC. The results of RT-qPCR and immunohistochemistry or Western blot demonstrated that BARX2 was reduced in NPC patients and cells. Ectopic expression of BARX2 reverted the malignant phenotype of NPC cells. Mechanistically, BARX2 bound to the keratin 16 (KRT16) promoter to downregulate its expression. In addition, BARX2 was found to reduce the phosphorylation levels of MEK and ERK. Further KRT16 upregulation in cells overexpressing BARX2 promoted malignant aggressiveness of C666-1 and HNE3 cells and activated the Ras signaling pathway. BARX2 inhibited the growth and metastasis of tumors and suppressed the Ras signaling pathway in vivo. In conclusion, our findings indicate that BARX2 reverts malignant phenotypes of NPC cells by downregulating KRT16 in a Ras-dependent fashion. BARX2 might act as a possible therapeutic regulator for NPC.
摘要：
鼻咽癌（NPC）是指由鼻咽上粘膜上皮引起的恶性肿瘤。仍然需要针对NPC的最佳疗法。在这次调查中,我们试图探索BarH-likehomeobox2(BARX2)，一种众所周知的肿瘤抑制剂，对NPC有抗癌作用，以及可能的机制。搜索与NPC相关的数据库后，我们确定BARX2是NPC的核心基因之一。RT-qPCR和免疫组织化学或Westernblot的结果表明，BARX2在NPC患者和细胞中降低。BARX2的异位表达逆转了NPC细胞的恶性表型。机械上,BARX2与角蛋白16(KRT16)启动子结合以下调其表达。此外,发现BARX2降低MEK和ERK的磷酸化水平。在过表达BARX2的细胞中KRT16的进一步上调促进了C666-1和HNE3细胞的恶性侵袭性并激活了Ras信号通路。BARX2在体内抑制肿瘤的生长和转移，抑制Ras信号通路。总之,我们的发现表明,BARX2通过以Ras依赖性方式下调KRT16,从而恢复NPC细胞的恶性表型.BARX2可能作为NPC的治疗调节因子。
