Department of Medical Imaging, Cancer Hospital of China Medical University, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, China.
Department of Medical Imaging, Liaoning Cancer Hospital and Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, China.
BMC Cancer. 2019 Jul 25;19(1):736. doi: 10.1186/s12885-019-5944-2.
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. Therefore, the purpose of this research was to determine the expression pattern and function of SETD5 in NSCLC.
SETD5 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.
Online 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.
These 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.
SET 结构域包含蛋白 5（SETD5）与前列腺癌和乳腺癌的侵袭性有关，但它与非小细胞肺癌（NSCLC）的关系尚不清楚。因此，本研究旨在确定 SETD5 在 NSCLC 中的表达模式和功能。
采用免疫组织化学分析方法检测 147 例非小细胞肺癌患者的 SETD5。在 A549 细胞中转染 SETD5 过表达质粒或在 H1299 细胞中转染 SETD5 干扰 RNA，划痕愈合和 Transwell 实验检测细胞迁移和侵袭能力，Western blot 检测 SETD5、p-AKT/AKT、Snail、p-JNK/JNK、Slug、E-cadherin、Zo-1、p-P38/P38、occludin、α-catenin、p-ERK/ERK、p-P90RSK/P90RSK 的表达水平。
对 1928 例 NSCLC 患者的总生存时间进行在线分析显示，SETD5 基因与总生存时间（OS）较差相关（P<0.001）。非癌组织中 SETD5 的阳性表达率低于癌组织（16.7%比 44.2%，P<0.001）。SETD5 与晚期 TNM 分期（P<0.001）、淋巴结转移（P<0.001）和总生存率（P<0.001）显著相关。在 A549 细胞中转染 SETD5 过表达质粒可增加细胞迁移和侵袭能力，而在 H1299 细胞中转染 SETD5 干扰 RNA 则降低细胞迁移和侵袭能力。过表达 SETD5 后，ZO-1 的表达下调，Snail 的表达上调。过表达 SETD5 后，p-ERK 及其下游因子 p-p90rsk 的水平增加。
这些结果表明，SETD5 可调节 p-P90RSK，促进 NSCLC 的迁移和侵袭，可能与 NSCLC 患者的不良预后有关。
