m6A 甲基转移酶 METTL14 通过调控 PI3K/AKT/mTOR 信号通路抑制胃癌的增殖、迁移和侵袭。
The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway.
机构信息
Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Department of Surgical Oncology and General Surgery, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Toxicology, School of Public Health, China Medical University, Shenyang, China.
出版信息
J Clin Lab Anal. 2021 Mar;35(3):e23655. doi: 10.1002/jcla.23655. Epub 2020 Dec 12.
BACKGROUND
N6-methyladenosine (m6A) modification may participate in the regulation of occurrence and development of tumors. However, the m6A level and the potential regulatory mechanism of m6A in gastric cancer (GC) remain uncertain.
METHODS
RNA m6A quantification assay was conducted to detect the m6A level in GC tissues and cell lines. Methyltransferase-like 14 (METTL14) expression in GC tissues was explored by bioinformatics and immunohistochemistry. Then, the function of METTL14 in GC cells was examined by CCK-8, colony formation assay, wound healing assay, and Transwell assay. Besides, Western blotting was conducted to probe the PI3K/AKT/mTOR pathway and the epithelial-mesenchymal transformation (EMT) pathway-related gene expression.
RESULTS
The m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 was downregulated in GC by analyzing both clinical samples and bioinformatics. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3K/AKT/mTOR pathway and the EMT pathway, respectively.
CONCLUSIONS
Our findings indicate that METTL14 partakes in the biological process of GC as a tumor suppressor and may be an emerging biomarker in GC.
背景
N6-甲基腺苷（m6A）修饰可能参与肿瘤的发生和发展的调控。然而，胃癌（GC）中 m6A 水平及其潜在的调控机制仍不确定。
方法
通过 RNA m6A 定量分析检测 GC 组织和细胞系中的 m6A 水平。通过生物信息学和免疫组织化学探讨 GC 组织中甲基转移酶样蛋白 14（METTL14）的表达。然后，通过 CCK-8、集落形成实验、划痕愈合实验和 Transwell 实验检测 METTL14 在 GC 细胞中的功能。此外，通过 Western blot 检测 PI3K/AKT/mTOR 通路和上皮-间充质转化（EMT）通路相关基因的表达。
结果
GC 中 m6A 修饰水平降低，METTL14 是导致 GC 中 m6A 紊乱的关键调节因子。通过分析临床样本和生物信息学，发现 METTL14 在 GC 中下调。METTL14 过表达通过抑制 PI3K/AKT/mTOR 通路和 EMT 通路分别抑制 GC 细胞增殖和侵袭。
结论
我们的研究结果表明，METTL14 作为一种肿瘤抑制因子参与 GC 的生物学过程，可能是 GC 的一种新兴生物标志物。
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