HOXA13 upregulation in gastric cancer is associated with enhanced cancer cell invasion and epithelial-to-mesenchymal transition

摘要

OBJECTIVE: In this study, we investigated the association between HOXA13 dysregulation and gastric cancer progression. We also explored the functional role of HOXA13 in invasion and epithelial-to-mesenchymal transition (EMT) of gastric cancer cells and the possible signaling pathway it might involve in. MATERIALS AND METHODS: The microarray (E-GEOD-19826) examined the transcription profiles of 12 adjacent normal/tumor-matched gastric tissues was downloaded from the ArrayExpress and reanalyzed. Immunohistochemistry (IHC) staining was performed to assess HOXA13 expression in 23 stage I and 69 stage II/III/IV gastric cancer tissues. The human gastric cancer cell line AGS and SGC-7901 cells were transfected with HOXA13 siRNA and then were subjected to detection of epithelial and mesenchymal markers and cell invasion. The involvement of HOXA13 in TGF-β signaling was further studied. RESULTS: HOXA13 is one of the most upregulated genes in gastric cancer tissues compared to adjacent normal tissues. Also, HOXA13 is further upregulated in the higher stage tumors. HOXA13 staining was significantly stronger in stage II/III/IV tumors than in stage I tumors. HOXA13 siRNA significantly restored the epithelial property and reduced the mesenchymal property of the cancer cells. Transwell assay showed that HOXA13 siRNA impaired the invasion capability of the cancer cells. The gastric cancer cells with HOXA13 knockdown had decreased expression of p-SMAD2 and p-SMAD3. CONCLUSIONS: This study provides additional evidence about the association between HOXA13 upregulation and gastric cancer progression. Also, we showed that HOXA13 contributes to invasion and EMT of gastric cancer cells via the TGF-b signaling pathway.