m6A-mediated ZNF750 repression facilitates nasopharyngeal carcinoma progression

m6A 介导的 ZNF750 抑制促进鼻咽癌进展

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作者:Panpan Zhang #, Qiuping He #, Yuan Lei #, Yingqin Li, Xin Wen, Mengzhi Hong, Jian Zhang, Xianyue Ren, Yaqin Wang, Xiaojing Yang, Qingmei He, Jun Ma, Na Liu

Abstract

Nasopharyngeal carcinoma (NPC) progression is regulated by genetic, epigenetic, and epitranscript modulation. As one of the epitranscript modifications, the role of N6-Methyladenosine (m6A) has not been elucidated in NPC. In the present study, we found that the poorly methylated gene ZNF750 (encoding zinc finger protein 750) was downregulated in NPC tumor tissues and cell lines. Ectopic expression of ZNF750 blocked NPC growth in vitro and in vivo. Further studies revealed that m6A modifications maintained the low expression level of ZNF750 in NPC. Chromatin immunoprecipitation sequencing identified that ZNF750 directly regulated FGF14 (encoding fibroblast growth factor 14), ablation of which reversed ZNF750's tumor repressor effect. Moreover, the ZNF750-FGF14 signaling axis inhibited NPC growth by promoting cell apoptosis. These findings uncovered the critical role of m6A in NPC, and stressed the regulatory function of the ZNF750-FGF14 signaling axis in modulating NPC progression, which provides theoretical guidance for the clinical treatment of NPC.

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