Liu Fang, Jin Sheng
Department of Respiratory and Critical Care Medicine, Hubei No. 3, People's Hospital of Jianghan University, No.26, Zhongshan Avenue, Qiaokou District, Wuhan, 430033, Hubei, China.
Department of Nephrology, Rheumatology and Immunology, Hubei No. 3, People's Hospital of Jianghan University, No.26, Zhongshan Avenue, Qiaokou District, Wuhan, 430033, Hubei, China.
Cell Div. 2025 May 22;20(1):12. doi: 10.1186/s13008-025-00156-y.
METTL16 has recently emerged as an N6-methyladenosine (mA) methyltransferase that serves an integral role in tumor regulation. However, its involvement in lung adenocarcinoma (LUAD) remains unexamined. This investigation aims to explore METTL16's role and mechanism in LUAD progression.
The expression of METTL16 and G2 and S phase-expressed-1 (GTSE1) in LUAD was evaluated by qRT-PCR or western blotting. LUAD cell malignancy was checked by CCK-8, wound healing, and transwell invasion assays. The relationship among METTL16 and GTSE1 was determined via Pearson correlation analysis and MeRIP assay. The p53 pathway-related proteins were detected by western blotting, and cell cycle was analyzed by flow cytometry.
METTL16 was elevated in LUAD, and its silencing significantly reduced LUAD cell proliferation, migration, and invasion. GTSE1 was significantly downregulated upon silencing METTL16. Furthermore, increased levels of GTSE1 mRNA and protein were found in LUAD, and it was correlated positively with METTL16 in LUAD tissues. The stability of GTSE1 was modulated by METTL16 in an mA-dependent way, and GTSE1 overexpression partially rescued the suppressive effects METTL16 silencing on LUAD cells. In addition, GTSE1 overexpression also inhibited p53 pathway to promote LUAD cell cycle.
These results indicate that METTL16-mediated mA modification of GTSE1 accelerates LUAD progression by regulating p53 pathway and cell cycle. The aforementioned findings suggest METTL16 and GTSE1 may serve as potential targets for LUAD management.
METTL16最近作为一种N6-甲基腺苷（m6A）甲基转移酶出现，在肿瘤调节中发挥着不可或缺的作用。然而，其在肺腺癌（LUAD）中的作用尚未得到研究。本研究旨在探讨METTL16在LUAD进展中的作用及机制。
通过qRT-PCR或蛋白质印迹法评估LUAD中METTL16和G2及S期表达蛋白1（GTSE1）的表达。通过CCK-8、伤口愈合和Transwell侵袭实验检测LUAD细胞的恶性程度。通过Pearson相关分析和MeRIP实验确定METTL16与GTSE1之间的关系。通过蛋白质印迹法检测p53通路相关蛋白，并通过流式细胞术分析细胞周期。
METTL16在LUAD中表达升高，其沉默显著降低了LUAD细胞的增殖、迁移和侵袭能力。沉默METTL16后，GTSE1显著下调。此外，在LUAD中发现GTSE1的mRNA和蛋白水平升高，且在LUAD组织中与METTL16呈正相关。METTL16以m6A依赖的方式调节GTSE1的稳定性，GTSE1过表达部分挽救了METTL16沉默对LUAD细胞的抑制作用。此外，GTSE1过表达还抑制p53通路以促进LUAD细胞周期。
这些结果表明，METTL16介导的GTSE1的m6A修饰通过调节p53通路和细胞周期加速LUAD进展。上述发现表明，METTL16和GTSE1可能作为LUAD治疗的潜在靶点。
