Abstract
BackgroundSET domain containing 5 (SETD5) is related to the aggressiveness of prostate and mammary cancers, but its association with non-small cell lung cancer (NSCLC) is unknown. Therefore, the purpose of this research was to determine the expression pattern and function of SETD5 in NSCLC.MethodsSETD5 was detected by immunohistochemical analysis in 147 patients with non-small cell lung cancer. SETD5 was overexpressed in A549 cells or suppressed with siRNA in H1299 cells. Wound healing and transwell assays were performed. The expression levels of SETD5, p-AKT/AKT, Snail, p-JNK/JNK, Slug, E-cadherin, Zo-1, p-P38/P38, occludin, α-catenin, p-ERK/ERK, and p-P90RSK/ P90RSK were assessed by western blot.ResultsOnline analysis of overall survival in 1928 patients with NSCLC showed that the SETD5 gene was related to worse overall survival (OS)(P < 0.001). The positive expression rate of SETD5 in noncancerous tissues was lower than that in cancerous tissues (16.7% vs. 44.2%, P < 0.001). SETD5 was significantly correlated with advanced TNM stage (P < 0.001), lymph node metastasis (P < 0.001) and overall survival rate (P < 0.001). Overexpression of SETD5 in A549 cells increased migration and invasion, while deletion of SETD5 in H1299 cells decreased migration and invasion. After overexpression of SETD5, the expression of ZO-1 was downregulated, and that of Snail was upregulated. After overexpression of SETD5, the levels of p-ERK and its downstream factor p-p90rsk increased.ConclusionThese results suggest that SETD5 could regulate p-P90RSK and facilitate the migration and invasion of NSCLC and may be related to the poor prognosis of patients with NSCLC.
Highlights
SET domain containing 5 (SETD5) is related to the aggressiveness of prostate and mammary cancers, but its association with non-small cell lung cancer (NSCLC) is unknown
The results showed that SETD5 enhanced the invasion of NSCLC cells by activating the ERK signaling pathway, suggesting that SETD5 may be a therapeutic target for NSCLC patients
SETD5 is related to worse overall survival in 1928 NSCLC patients from a public database To preliminarily examine the potential role of SETD5 in NSCLC, the online tool KM plotter was used to predict the effect of SETD5 gene expression on OS in 1928 patients with NSCLC
Summary
SET domain containing 5 (SETD5) is related to the aggressiveness of prostate and mammary cancers, but its association with non-small cell lung cancer (NSCLC) is unknown. Non-small cell lung cancer (NSCLC) is a malignant tumor of the lung accounting for 85–90% of all lung cancers [1]. It affects mainly adults > 65 years of age, men, and tobacco smokers [1, 2]. Despite great advances in techniques, regimens, and targeted therapies, the 5-year survival for patients with NSCLC (all stages together) is only 18% [4], highlighting the need to better understand the disease to further improve the treatment strategies
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