Department of General Surgery, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Department of Intensive Care Unit, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Acta Biochim Biophys Sin (Shanghai). 2018 May 1;50(5):440-446. doi: 10.1093/abbs/gmy026.
Acidic microenvironment, particularly acid-sensing ion channel 1a (ASIC1a), has been reported to promote carcinoma cell proliferation as well as migration. In this study, we explored the effect of ASIC1a on migration and invasion of gastric carcinoma (GC). ASIC1a expression levels were examined in paired GC and adjacent normal tissues from 16 patients by immunohistochemistry. Reverse transcription real-time PCR and immunoblotting were conducted to assess the ASIC1a expression levels in the GC cell line AGS after transfection with ASIC1a small hairpin RNA (shRNA). Wound healing and transwell invasion assays were utilized to detect metastasis and invasion following ASIC1a silencing. Tumor formation was used to detect the role of ASIC1a in tumorigenicity in vivo. It was found that ASIC1a expression level was significantly higher in GC tissues showing postoperative metastasis compared with non-metastasis and non-tumor tissues. Moreover, silencing of ASIC1a with shRNA significantly down-regulated ASIC1a expression and reduced GC cell migration and invasion. A moderately acidic extracellular environment inhibited GC cell viability. Furthermore, ASIC1a shRNA caused inhibition of tumorigenicity in vivo. Our study is the first report of attenuating the malignant phenotype of GC in vitro and in vivo by suppressing ASIC1a, and suggests a novel approach to study the relationship between ASICs and GC cell migration and invasion.
酸性微环境，特别是酸感应离子通道 1a（ASIC1a），已被报道可促进癌细胞增殖和迁移。在这项研究中，我们探讨了 ASIC1a 对胃癌（GC）迁移和侵袭的影响。通过免疫组织化学法检测了 16 例患者配对的 GC 和相邻正常组织中的 ASIC1a 表达水平。通过转染 ASIC1a 短发夹 RNA（shRNA），对 GC 细胞系 AGS 中的 ASIC1a 表达水平进行了逆转录实时 PCR 和免疫印迹检测。通过划痕愈合和 Transwell 侵袭实验检测了 ASIC1a 沉默后转移和侵袭的情况。通过肿瘤形成实验检测了 ASIC1a 在体内致瘤性中的作用。结果发现，与无转移和无肿瘤组织相比，术后发生转移的 GC 组织中 ASIC1a 的表达水平显著升高。此外，用 shRNA 沉默 ASIC1a 可显著下调 ASIC1a 的表达，并降低 GC 细胞的迁移和侵袭。中等酸性细胞外环境可抑制 GC 细胞活力。此外，ASIC1a shRNA 导致体内肿瘤生成能力受到抑制。我们的研究首次报道了通过抑制 ASIC1a 在体外和体内减弱 GC 的恶性表型，并提示了研究 ASICs 与 GC 细胞迁移和侵袭之间关系的新方法。
