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

Abstract

Su(var)3-9, enhancer of zeste, Trithorax] domaincontaining 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.

Long non-coding RNA LINC01194 promotes the proliferation, migration and invasion of lung adenocarcinoma cells by targeting miR-641/SETD7 axis

“…However, with respect to the role of SETD7 in lung cancer, there is a dispute over this matter in the current literatures. Cao et al unveiled that SETD7 is downregulated in LUAD and has restraining effects on LUAD cell migration and invasion [29]. In contrast, Fu et al argue that SETD7 activates Hedgehog pathway to aggravate the tumorigenesis of NSCLC [8], and Lezina et al believe that SEDT7 contributes to cell proliferation in lung tumors [30].…”

Autophagic secretion of HMGB1 from cancer-associated fibroblasts promotes metastatic potential of non-small cell lung cancer cells via NFκB signaling

“…Cell migration ability was assessed by the wound healing experiment as previously described [ 20 ]. Briefly, A549 and H661 cells were plated in six-well plates and cultured under different conditions for 24 h. A linear scratch was generated on the cell monolayer using a pipette tip.…”

The Double Face of Glioma Exosomal microRNAs: Glioma Eliminates Tumor Suppressor miR-1298-5p via Exosomes to Promote Immunosuppressive Effects of MDSCs

“…SETD7 (also known as SET7, SET9, or SET7/9) is a methyltransferase for H3K4 and belongs to the SET domain-containing proteins, which is related to demethylation of H3K4 (H3K4me2) and induces downstream gene expression. It has been reported that SETD7 plays a critical role in hepatocellular carcinoma, colorectal cancer, lung cancer and so on (35)(36)(37)(38). In this study, we found that SETD7 knockdown inhibited the proliferation of glioma via AKT pathway.…”