2. Academic Validation
  3. SMYD2 promotes tumorigenesis and metastasis of lung adenocarcinoma through RPS7

SMYD2 promotes tumorigenesis and metastasis of lung adenocarcinoma through RPS7

  • Cell Death Dis. 2021 May 2;12(5):439. doi: 10.1038/s41419-021-03720-w.
Lei Wu  # 1 2 3 4 5,  Fan Kou  # 1 2 3 4 5,  Zhenyu Ji 1 2 3 4 5,  Baihui Li 1 2 3 4 5,  Bailu Zhang 1 2 3 4 5,  Yan Guo 1 2 3 4 5,  Lili Yang 6 7 8 9 10
Affiliations

Affiliations

  • 1 Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
  • 2 National Clinical Research Center for Cancer, Tianjin, China.
  • 3 Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
  • 4 Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
  • 5 Tianjin's Clinical Research Center for Cancer, Tianjin, China.
  • 6 Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. yanglili@tjmuch.com.
  • 7 National Clinical Research Center for Cancer, Tianjin, China. yanglili@tjmuch.com.
  • 8 Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China. yanglili@tjmuch.com.
  • 9 Key Laboratory of Cancer Prevention and Therapy, Tianjin, China. yanglili@tjmuch.com.
  • 10 Tianjin's Clinical Research Center for Cancer, Tianjin, China. yanglili@tjmuch.com.
  • # Contributed equally.
PMID: 33935284 DOI: 10.1038/s41419-021-03720-w
Abstract

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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