Department of Otolaryngology, Airborne Army Hospital, Wuhan 430012, Hubei, China.
Department of Otolaryngology Head and Neck Surgery, Wuhan Asia General Hospital, Wuhan 430056, Hubei, China.
Crit Rev Immunol. 2023;43(4):15-27. doi: 10.1615/CritRevImmunol.2023050249.
Emerging evidence suggests that dysregulation of a N6-methyladenosine (m6A) methyltransferase KIAA1429 participates in the pathogenesis of multiple cancers except for nasopharyngeal carcinoma (NPC). This study is aimed to explore the function of KIAA1429 in NPC progression. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to confirm the mRNA expression in NPC by bioinformatic analysis. The levels of KIAA1429 and PTGS2 was detected by quantitative reverse transcription polymerase chain reaction and Western blotting. To investigate the effects of KIAA1429/PTGS2 knockdown or overexpression vectors on NPC cell malignancy, cell and animal experiments were performed. Finally, MeRIP and mRNA stability assays were used to verify the m6A modification and mRNA stability, respectively. KIAA1429 was upregulated in NPC tissues and cells. After transfecting KIAA1429 knockdown or overexpression vectors in NPC cells, we proved that KIAA1429 overexpression promoted proliferation, migration, invasion, and tumor growth, whereas KIAA1429 knockdown showed the opposite effect. Our results also indicated that KIAA1429 mediated m6A modification of PTGS2, enhancing PTGS2 mRNA stability in NPC cells. In addition, PTGS2 could also regulate the effects of KIAA1429 on NPC cell malignancy. This study confirmed the oncogenic function of KIAA1429 in NPC through m6A-modification of PTGS2, suggesting that targeting KIAA1429-mediated m6A modification of PTGS2 might provide a new therapeutic strategy for NPC.
新出现的证据表明,N6-甲基腺苷(m6A)甲基转移酶 KIAA1429 的失调参与了多种癌症的发病机制,鼻咽癌(NPC)除外。本研究旨在探讨 KIAA1429 在 NPC 进展中的作用。通过生物信息学分析,利用癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)数据集来确认 NPC 中的 mRNA 表达。通过定量逆转录聚合酶链反应和 Western blot 检测 KIAA1429 和 PTGS2 的水平。为了研究 KIAA1429/PTGS2 敲低或过表达载体对 NPC 细胞恶性的影响,进行了细胞和动物实验。最后,使用 MeRIP 和 mRNA 稳定性测定分别验证 m6A 修饰和 mRNA 稳定性。KIAA1429 在 NPC 组织和细胞中上调。在 NPC 细胞中转染 KIAA1429 敲低或过表达载体后,我们证明 KIAA1429 过表达促进了增殖、迁移、侵袭和肿瘤生长,而 KIAA1429 敲低则表现出相反的效果。我们的结果还表明,KIAA1429 介导了 PTGS2 的 m6A 修饰,增强了 NPC 细胞中 PTGS2 mRNA 的稳定性。此外,PTGS2 也可以调节 KIAA1429 对 NPC 细胞恶性的影响。本研究通过 PTGS2 的 m6A 修饰证实了 KIAA1429 在 NPC 中的致癌作用,表明靶向 KIAA1429 介导的 PTGS2 的 m6A 修饰可能为 NPC 提供一种新的治疗策略。