m6A-mediated ZNF750 repression facilitates nasopharyngeal carcinoma progression

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.

Effect of m6A RNA Methylation Regulators on Malignant Progression and Prognosis in Renal Clear Cell Carcinoma

“…High expression of YTHDF1 was found to be associated with advanced stages and unfavorable prognosis in hepatocellular carcinoma (30). The key role of m 6 A RNA methylation regulators are also noted in different cancers, such as lung cancer (31), bladder cancer (32), and nasopharyngeal carcinoma (33). Recently, a research focused on the mutations and copy number variants of 10 m 6 A regulatory genes in ccRCC and found copy number variants of these regulatory genes closely correlated with pathologic stage and prognosis of patients with ccRCC (34).…”

Fibroblast Growth Factor—14 Acts as Tumor Suppressor in Lung Adenocarcinomas

“…FGF14-b is primarily located in the cytoplasm, and FGF14-a can bind to DNA and is found in the nucleus [18,23]. FGF14 expression is altered in various tumors [24][25][26] and it has been suggested to regulate apoptosis and proliferation in nasopharyngeal carcinoma and colorectal cancer [26,27]. Nonetheless, the role of FGF14 in lung cancer, especially in NSCLC remains unelucidated.…”

Contributions and prognostic values of m6A RNA methylation regulators in non‐small‐cell lung cancer

“…METTL3 was upregulated in AML (Barbieri et al, 2017; Vu et al, 2017), bladder cancer (Cheng et al, 2019), breast cancer (Cai et al, 2018), HCC (Chen et al, 2018), and lung cancer (Liu et al, 2018). In contrast, downregulation of METTL3 in nasopharyngeal carcinoma (Zhang et al, 2018), METTL3/METTL14 in glioblastoma (Cui et al, 2017) and endometrial cancer (Liu et al, 2018), and WTAP in AML (Bansal et al, 2014) and CRC (Zhang et al, 2016) were also reported.…”