Downregulation of SETD7 promotes migration and invasion of lung cancer cells via JAK2/STAT3 pathway

  • Authors:
    • Limin Cao
    • Yinghui Ren
    • Xueru Guo
    • Limin Wang
    • Qicheng Zhang
    • Xueqin Li
    • Xiang Wu
    • Zhaowei Meng
    • Ke Xu
  • View Affiliations

  • Published online on: March 3, 2020     https://doi.org/10.3892/ijmm.2020.4523
  • Pages: 1616-1626
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Abstract

[Su(var)3‑9, enhancer of zeste, Trithorax] domain‑​containing protein 7 (SETD7) is a protein lysine methyltransferase that methylates both histone H3K4 and non‑histone proteins, such as transcription factors. The methylation on proteins alters their activity and affects a series of biological processes. Recent studies have demonstrated that SETD7 contributes to tumor progression and may play different roles in tumor development. However, the effect of SETD7 on lung cancer cell migration and invasion has not been fully elucidated. The present study demonstrated that the expression of SETD7 was significantly downregulated in lung cancer tissues in comparison with that in matched non‑cancer tissues, and lung cancer cell lines also exhibited lower SETD7 levels compared with normal human bronchial epithelial cells. Overexpression of SETD7 inhibited the migration and invasion of lung cancer cells, whereas decreased SETD7 expression promoted cell migration and invasion. Further study revealed that SETD7 regulated the expression of the metastasis‑related genes metalloproteinase 2, Twist1 and vascular endothelial growth factor. Furthermore, SETD7 knockdown activated the Janus kinase 2/signal transducer and activator of transcription 3 (STAT3) signaling pathway and enhanced lung cancer cell migration, whereas the STAT3‑specific inhibitor Stattic abrogated the effect of SETD7 on cell migration. Taken together, these data indicated that SETD7 acts as a tumor suppressor, and the reduced expression of SETD7 may contribute to lung cancer progression. The findings of the present study suggest that SETD7 may be a novel candidate for the treatment of metastatic lung cancer.

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May 2020
Volume 45 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Cao, L., Ren, Y., Guo, X., Wang, L., Zhang, Q., Li, X. ... Xu, K. (2020). Downregulation of SETD7 promotes migration and invasion of lung cancer cells via JAK2/STAT3 pathway. International Journal of Molecular Medicine, 45, 1616-1626. https://doi.org/10.3892/ijmm.2020.4523
MLA
Cao, L., Ren, Y., Guo, X., Wang, L., Zhang, Q., Li, X., Wu, X., Meng, Z., Xu, K."Downregulation of SETD7 promotes migration and invasion of lung cancer cells via JAK2/STAT3 pathway". International Journal of Molecular Medicine 45.5 (2020): 1616-1626.
Chicago
Cao, L., Ren, Y., Guo, X., Wang, L., Zhang, Q., Li, X., Wu, X., Meng, Z., Xu, K."Downregulation of SETD7 promotes migration and invasion of lung cancer cells via JAK2/STAT3 pathway". International Journal of Molecular Medicine 45, no. 5 (2020): 1616-1626. https://doi.org/10.3892/ijmm.2020.4523