Liu Gang, Guo Zhongliang, Zhang Qian, Liu Zhongmin, Zhu Dongyi
Department of Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, People's Republic of China.
Department of Respiratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, People's Republic of China.
Onco Targets Ther. 2020 Dec 16;13:12893-12903. doi: 10.2147/OTT.S281517. eCollection 2020.
Lung adenocarcinoma is one of the common causes of cancer-related deaths worldwide. are giant proteins, which are correlated with cell structure and migration, cardiac calcium channel signaling, and other processes. Current studies identified as a novel oncogene in some cancers; however, studies on its function in lung cancers are limited.
The expression of was analyzed in normal lung tissues, lung adenocarcinoma tissues, and paracancerous tissues using the Oncomine database. It was further verified in relative cell lines by real-time quantitative polymerase chain reaction and Western blotting (WB). Adenocarcinoma cell lines were transfected with si-NC and si- by lipofectamine 3000 and treated with or without TGF-β1, and cell migration and invasion were detected by wound-healing and transwell assays. The expression of epithelial-mesenchymal transition (EMT) markers was detected by WB, as well as that of phosphorylated-Smad3 (p-Smad3) and Smad3 levels. After Smad3 phosphorylation inhibitor was added to the adenocarcinoma cell lines, migration and invasion were detected by wound-healing and transwell assays, and the expression of EMT markers was detected by WB when the cells were transfected with si-NC and si- and treated with or without TGF-β1.
We found higher expression of in lung adenocarcinoma tissues through the Oncomine database and further verified its high expression in relative cell lines. When the cells were stimulated with TGF-β1, knockdown of suppressed cell migration, invasion, and EMT, and inhibited TGF-β-induced Smad3 signaling. When p-Smad3 was inhibited, knockdown of had no effect on the two cell lines investigated when treated with or without TGF-β1.
acts as an oncogenic protein and promotes migration, invasion, and EMT in lung adenocarcinoma cells via the TGF-β/Smad3 pathway. Thus, it may be a novel target for lung adenocarcinoma therapy.
肺腺癌是全球癌症相关死亡的常见原因之一。[相关蛋白名称]是巨大的蛋白质，与细胞结构和迁移、心脏钙通道信号传导及其他过程相关。目前的研究已确定[相关蛋白名称]在某些癌症中是一种新型致癌基因；然而，关于其在肺癌中功能的研究有限。
使用Oncomine数据库分析[相关蛋白名称]在正常肺组织、肺腺癌组织和癌旁组织中的表达。通过实时定量聚合酶链反应和蛋白质免疫印迹法（WB）在相关细胞系中进一步验证。用脂质体3000将腺癌细胞系转染si-NC和si-[相关蛋白名称]，并在有或无转化生长因子-β1（TGF-β1）的情况下进行处理，通过伤口愈合试验和Transwell试验检测细胞迁移和侵袭。通过WB检测上皮-间质转化（EMT）标志物的表达，以及磷酸化Smad3（p-Smad3）和Smad3的水平。在腺癌细胞系中加入Smad3磷酸化抑制剂后，通过伤口愈合试验和Transwell试验检测迁移和侵袭，并在细胞转染si-NC和si-[相关蛋白名称]且有或无TGF-β1处理时，通过WB检测EMT标志物的表达。
我们通过Oncomine数据库发现肺腺癌组织中[相关蛋白名称]表达较高，并在相关细胞系中进一步验证了其高表达。当细胞用TGF-β1刺激时，敲低[相关蛋白名称]可抑制细胞迁移、侵袭和EMT，并抑制TGF-β诱导的Smad3信号传导。当p-Smad3被抑制时，敲低[相关蛋白名称]对所研究的两种细胞系在有或无TGF-β1处理时均无影响。
[相关蛋白名称]作为一种致癌蛋白，通过TGF-β/Smad3途径促进肺腺癌细胞的迁移、侵袭和EMT。因此，它可能是肺腺癌治疗的一个新靶点。
