Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
National Clinical Research Center for Cancer, Tianjin, China.
Cell Death Dis. 2021 May 2;12(5):439. doi: 10.1038/s41419-021-03720-w.
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.
蛋白质甲基转移酶 SET 和 MYND 结构域包含蛋白 2（SMYD2）是一种转录调节剂，可甲基化组蛋白和非组蛋白蛋白。作为一种癌基因，SMYD2 已在多种类型的癌症中得到研究。然而，它在肺癌中的作用仍不清楚。通过生物信息学分析、逆转录聚合酶链反应、western blot 和免疫组织化学，确定了 SMYD2 在肺腺癌（LUAD）中的表达的预后价值。在体内和体外研究了 SMYD2 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 研究了其潜在机制。SMYD2 的表达在 LUAD 细胞系和组织中明显上调。SMYD2 高表达与 LUAD 患者的总生存期和无病生存期缩短相关。SMYD2 敲低或 AZ505 抑制 SMYD2 的表达，可显著抑制 GLC-82 和 SPC-A1 细胞的增殖、迁移和侵袭能力，并显著抑制小鼠肿瘤生长。在机制上，SMYD2 可能通过结合其启动子来激活核糖体小亚基蛋白 7（RPS7）的转录。过表达 SMYD2 后，细胞的增殖、迁移和侵袭增加，而 RPS7 部分逆转了这一过程。因此，SMYD2 可能通过调节 RPS7 介导的 LUAD 肿瘤发生和转移。SMYD2 可能是 LUAD 的预后生物标志物和治疗靶点。
