miR-339-3p 通过调控 KAT6A/TRIM24 轴抑制鼻咽癌细胞生长和上皮间质转化。
miR-339-3p inhibits cell growth and epithelial-mesenchymal transition in nasopharyngeal carcinoma by modulating the KAT6A/TRIM24 axis.
机构信息
Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jianshe Road, Erqi District, Zhengzhou, Henan, 450052, People's Republic of China.
Department of Otology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China.
出版信息
Int J Clin Oncol. 2022 Nov;27(11):1684-1697. doi: 10.1007/s10147-022-02231-8. Epub 2022 Aug 17.
OBJECTIVE
To explore the effect and mechanism of the miR-339-3p/KAT6A/TRIM24 axis in nasopharyngeal carcinoma (NPC) cell growth and epithelial-mesenchymal transition (EMT) progression.
METHODS
CNE2 and 5-8F NPC cell lines were transfected with miR-339-3p-mimic or sh-KAT6A alone or co-transfected with miR-339-3p-mimic and oe-KAT6A. The expression levels of miR-339-3p, KAT6A, TRIM24, and EMT-related proteins were assessed, in addition to cell biological behaviors. Then, the relationship between miR-339-3p and KAT6A was predicted and validated. The correlations between miR-339-3p and KAT6A or between KAT6A and TRIM24 were analyzed by Pearson coefficient and the enrichment of H3K23ac in TRIM24 promoter region was measured by chromatin immunoprecipitation.
RESULTS
miR-339-3p was downregulated, but KAT6A and TRIM24 were highly expressed in NPC cells and tissues. Upregulated miR-339-3p or downregulated KAT6A could inhibit the growth and EMT of NPC cells. Further experiments showed that miR-339-3p regulated NPC cell growth and EMT by mediating KAT6A in a targeted fashion. KAT6A was positively correlated with TRIM24, and the enrichment of H3K23ac was much higher in NPC tissues. miR-339-3p suppressed the growth and EMT of NPC cells by the KAT6A/TRIM24 axis. In a xenograft study, miR-339-3p overexpression inhibited NPC tumor growth in vivo.
CONCLUSION
Conclusively, miR-339-3p inhibited the growth and EMT of NPC cells via the KAT6A/TRIM24 axis.
目的
探讨 miR-339-3p/KAT6A/TRIM24 轴在鼻咽癌细胞生长和上皮间质转化（EMT）进展中的作用及机制。
方法
单独转染 miR-339-3p 模拟物或 sh-KAT6A 或共转染 miR-339-3p 模拟物和 oe-KAT6A 转染 CNE2 和 5-8F 鼻咽癌细胞系。评估 miR-339-3p、KAT6A、TRIM24 和 EMT 相关蛋白的表达水平以及细胞生物学行为。然后，预测和验证 miR-339-3p 与 KAT6A 之间的关系。通过 Pearson 系数分析 miR-339-3p 与 KAT6A 或 KAT6A 与 TRIM24 之间的相关性，并通过染色质免疫沉淀测量 TRIM24 启动子区域中 H3K23ac 的富集。
结果
miR-339-3p 在 NPC 细胞和组织中表达下调，而 KAT6A 和 TRIM24 表达上调。上调 miR-339-3p 或下调 KAT6A 均可抑制 NPC 细胞的生长和 EMT。进一步的实验表明，miR-339-3p 通过靶向调节 KAT6A 来调节 NPC 细胞的生长和 EMT。KAT6A 与 TRIM24 呈正相关，并且 NPC 组织中 H3K23ac 的富集更高。miR-339-3p 通过 KAT6A/TRIM24 轴抑制 NPC 细胞的生长和 EMT。在异种移植研究中，miR-339-3p 的过表达抑制了 NPC 肿瘤在体内的生长。
结论
综上所述，miR-339-3p 通过 KAT6A/TRIM24 轴抑制 NPC 细胞的生长和 EMT。
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