Open AccessDownregulation of SETD7 promotes migration and invasion of lung cancer cells via JAK2/STAT3 pathway
Author(s) -
Limin Cao,
Yinghui Ren,
Xueru Guo,
Limin Wang,
Qicheng Zhang,
Xueqin Li,
Xiang Wu,
Zhaowei Meng,
Ke Xu
Publication year - 2020
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2020.4523
Subject(s) - cancer research , lung cancer , carcinogenesis , biology , stat3 , cell migration , cell cycle , cell , cell growth , cancer , signal transduction , pathology , medicine , microbiology and biotechnology , genetics
[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.