SMYD2 promotes tumorigenesis and metastasis of lung adenocarcinoma through RPS7.
SMYD2 promotes tumorigenesis and metastasis of lung adenocarcinoma through RPS7.
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SMYD2通过RPS7促进肺腺癌的肿瘤发生和转移。
DOI：
10.1038/s41419-021-03720-w
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发表时间：
2021-05-02
影响因子：
9
通讯作者：
Yang L
中科院分区：
文献类型：
--
作者：
Wu L;Kou F;Ji Z;Li B;Zhang B;Guo Y;Yang L
蛋白质甲基转移酶SET和MYND结构域包含蛋白2（SMYD 2）是甲基化组蛋白和非组蛋白的转录调节因子。作为一种癌基因，SMYD 2已在许多类型的癌症中进行了研究。然而，它与肺癌的关系仍然难以捉摸。通过生物信息学分析、逆转录聚合酶链反应、蛋白质印迹和免疫组化确定SMYD 2表达在肺腺癌（LUAD）中的预后价值。在体内和体外研究SMYD 2对LUAD细胞增殖和转移的影响，并通过RNA-seq和染色质免疫沉淀-定量PCR研究其潜在机制。SMYD 2表达在LUAD细胞系和组织中显著上调。在LUAD患者中，SMYD 2高表达与较短的总生存期和无病生存期相关。通过SMYD 2敲低或AZ 505抑制SMYD 2显著抑制GLC-82和SPC-A1细胞的增殖、迁移和侵袭能力，并显著降低小鼠肿瘤生长。在机械上，SMYD 2可以通过结合其启动子来激活核糖体小亚基蛋白7（RPS 7）的转录。在SMYD 2过表达后，细胞的增殖、迁移和侵袭增加，这被RPS 7部分逆转。因此，SMYD 2可能调节RPS 7 LUAD介导的肿瘤发生和转移。SMYD 2可能是LUAD的预后标志物和治疗靶点。
The protein methyltransferase SET and MYND domain-containing protein 2 (SMYD2) is a transcriptional regulator that methylates histones and nonhistone proteins. As an oncogene, SMYD2 has been investigated in numerous types of cancer. However, its involvement in lung cancer remains elusive. The prognostic value of SMYD2 expression in lung adenocarcinoma (LUAD) was determined through bioinformatics analysis, reverse-transcription polymerase chain reaction, western blotting, and immunohistochemistry. The effect of SMYD2 on LUAD cell proliferation and metastasis was explored in vivo and in vitro, and the underlying mechanisms were investigated via RNA-seq, and chromatin immunoprecipitation-quantitative PCR. SMYD2 expression was significantly upregulated in LUAD cell lines and tissues. High SMYD2 expression was associated with shorter overall and disease-free survival in LUAD patients. Inhibition of SMYD2 with SMYD2 knockdown or AZ505 dramatically inhibited the proliferation, migration, and invasion ability of GLC-82 and SPC-A1 cells and remarkably reduced tumor growth in mice. Mechanically, SMYD2 may activate the transcription of ribosomal small subunit protein 7 (RPS7) by binding to its promoter. Following overexpression of SMYD2, the proliferation, migration, and invasion of cells increased, which was partially reversed by RPS7. Thus, SMYD2 might modulate tumorigenesis and metastasis mediated by RPS7 LUAD. SMYD2 might be a prognostic biomarker and therapeutic target in LUAD.
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影响因子：
8.8
作者：
Komatsu S;Ichikawa D;Hirajima S;Nagata H;Nishimura Y;Kawaguchi T;Miyamae M;Okajima W;Ohashi T;Konishi H;Shiozaki A;Fujiwara H;Okamoto K;Tsuda H;Imoto I;Inazawa J;Otsuji E
通讯作者：
Otsuji E
影响因子：
2.6
作者：
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通讯作者：
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影响因子：
4
作者：
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通讯作者：
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影响因子：
3.5
作者：
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通讯作者：
Brown M
影响因子：
5.7
作者：
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通讯作者：
Keen, Nicholas