Conclusion
AHNAK2 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.
Methods
The expression of AHNAK2 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-AHNAK2 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-AHNAK2 and treated with or without TGF-β1.
Purpose
Lung adenocarcinoma is one of the common causes of cancer-related deaths worldwide. AHNAKs are giant proteins, which are correlated with cell structure and migration, cardiac calcium channel signaling, and other processes. Current studies identified AHNAK2 as a novel oncogene in some cancers; however, studies on its function in lung cancers are limited. Materials and
Results
We found higher expression of AHNAK2 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 AHNAK2 suppressed cell migration, invasion, and EMT, and inhibited TGF-β-induced Smad3 signaling. When p-Smad3 was inhibited, knockdown of AHNAK2 had no effect on the two cell lines investigated when treated with or without TGF-β1.