The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway.

The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway.
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m6 A甲基转移酶L14通过调节PI 3 K/AKT/mTOR信号通路抑制胃癌的增殖、迁移和侵袭。

DOI:
10.1002/jcla.23655
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发表时间:
2021-03
影响因子:
2.7
通讯作者:
Sun Z
Sun Z
中科院分区:
医学4区
文献类型:
--
作者:
Liu X;Xiao M;Zhang L;Li L;Zhu G;Shen E;Lv M;Lu X;Sun Z

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N6-甲基腺苷(m6 A)修饰可能参与调节肿瘤的发生和发展。然而,m6 A在胃癌(GC)中的水平及其潜在的调控机制仍不清楚。RNA m6 A定量分析检测胃癌组织和细胞系中m6 A的水平。通过生物信息学和免疫组织化学研究胃癌组织中甲基转移酶样14(胃L14)的表达。然后,通过CCK-8、集落形成试验、伤口愈合试验和Transwell试验检测胃L14在GC细胞中的功能。此外,通过Western blotting检测PI 3 K/AKT/mTOR通路和上皮-间质转化(EMT)通路相关基因的表达。胃癌中m6 A修饰水平降低,胃L14是导致胃癌m6 A紊乱的关键调节因子。通过分析临床样品和生物信息学,胃L14在GC中下调。胃L14过表达分别通过使PI 3 K/AKT/mTOR通路和EMT通路失活来抑制GC细胞增殖和侵袭。我们的研究结果表明,胃L14作为一种肿瘤抑制因子参与了胃癌的生物学过程,可能是一种新的胃癌生物标志物。胃L14作为肿瘤抑制因子抑制GC细胞的进展和侵袭。
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. 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. 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. Our findings indicate that METTL14 partakes in the biological process of GC as a tumor suppressor and may be an emerging biomarker in GC. METTL14 depresses GC cell progression and aggression as a tumor suppressor.
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