Department of General Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
Oncol Rep. 2018 Aug;40(2):1156-1164. doi: 10.3892/or.2018.6478. Epub 2018 Jun 7.
Gastric cancer is one of the most common and lethal malignancies globally, especially in East Asia. Although significant progress has been made in the diagnosis and treatment of the disease, the overall survival rate remains unchanged at 20‑25%. Thus, there is an urgent need for a better understanding of the disease. Recent years have witnessed the critical roles of aberrant cancer cell metabolism in the maintenance of malignant properties of cancer cells, and targeting cancer cell metabolism has been regarded as a novel aspect in the development of treatments against cancer. In the present study, we identified a novel gene, AAED1 (AhpC/TSA antioxidant enzyme domain containing 1), which is upregulated in gastric cancer cells. By using lentivirus mediated transfection method, we silenced AAED1 expression and silencing of AAED1 inhibited cancer cell proliferation in vitro in gastric cancer cell lines, as demonstrated by cell viability and colony formation assay. Furthermore, we uncovered novel functions of AAED1 in regulating hypoxia inducible factor 1α (HIF1α) and the resultant aerobic glycolysis, which was measured by extracellular flux analysis. Collectively, the results of the present study uncovered novel markers that could identify the possible molecular mechanisms involved in gastric cancer.
胃癌是全球最常见和最致命的恶性肿瘤之一,尤其在东亚地区。尽管在疾病的诊断和治疗方面取得了重大进展,但总体生存率仍保持在 20-25%不变。因此,迫切需要更好地了解这种疾病。近年来,癌细胞代谢异常在维持癌细胞恶性特性方面的关键作用已经得到证实,靶向癌细胞代谢已被视为开发癌症治疗方法的一个新方面。在本研究中,我们鉴定了一个在胃癌细胞中上调的新型基因 AAED1(含 AhpC/TSA 抗氧化酶结构域的 1)。通过慢病毒介导的转染方法,我们沉默了 AAED1 的表达,细胞活力和集落形成实验表明,沉默 AAED1 可抑制胃癌细胞系中的体外癌细胞增殖。此外,我们揭示了 AAED1 在调节缺氧诱导因子 1α(HIF1α)和随后的有氧糖酵解方面的新功能,这是通过细胞外通量分析来衡量的。总之,本研究的结果揭示了可能识别胃癌中涉及的潜在分子机制的新型标志物。