Department of Gastrointestinal Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).
Med Sci Monit. 2018 Oct 28;24:7689-7696. doi: 10.12659/MSM.910867.
BACKGROUND lncRNA GAS5 acts as a tumor-suppressor gene in various types of malignancies, but its involvement in esophageal cancer has not been well studied. MATERIAL AND METHODS A total of 112 patients with esophageal cancer and 55 volunteers with normal physiological conditions were included in this study. Tumor tissues and adjacent healthy tissues were collected from esophageal cancer patients and blood was extracted from patients and controls. Expression of GAS5 in those tissues was detected by qRT-PCR. All patients were followed up for 5 years and diagnostic and prognostic values of serum GAS5 for esophageal cancer were investigated by ROC curve analysis and survival curve analysis, respectively. Effects of GAS5 expression on cell proliferation and migration were investigated by CCK-8 assay and Transwell cell migration assay, respectively. Effects of GAS5 overexpression on expression of PI3K/AKT/mTOR-related proteins were explored by Western blot analysis. RESULTS GAS5 expression level was lower in tumor tissues than in adjacent healthy tissues. Serum level of GAS5 was lower in cancer patients than in healthy controls, and serum level of GAS5 was decreased with increase in stage of primary tumor (T stage). GAS5 overexpression inhibited tumor cell proliferation and migration, while treatment with PI3K activator reduced the inhibitory effects. GAS5 overexpression decreased the expression level of PI3K and phosphorylation levels of Akt and mTOR in esophageal cancer cells, while PI3K activator treatment showed no significant effects on GAS5 expression. CONCLUSIONS GAS5 was downregulated in esophageal cancer patients compared to healthy controls, and GAS5 overexpression suppressed proliferation and migration of esophageal cancer cells by inactivating the PI3K/AKT/mTOR pathway.
lncRNA GAS5 在多种恶性肿瘤中作为抑癌基因发挥作用，但它在食管癌中的作用尚未得到充分研究。
本研究共纳入 112 例食管癌患者和 55 例具有正常生理条件的志愿者。从食管癌患者中采集肿瘤组织和相邻的健康组织，从患者和对照者中提取血液。通过 qRT-PCR 检测这些组织中 GAS5 的表达。对所有患者进行 5 年随访，通过 ROC 曲线分析和生存曲线分析分别研究血清 GAS5 对食管癌的诊断和预后价值。通过 CCK-8 测定和 Transwell 细胞迁移测定分别研究 GAS5 表达对细胞增殖和迁移的影响。通过 Western blot 分析探讨 GAS5 过表达对 PI3K/AKT/mTOR 相关蛋白表达的影响。
肿瘤组织中的 GAS5 表达水平低于相邻的健康组织。癌症患者的血清 GAS5 水平低于健康对照组，且血清 GAS5 水平随原发肿瘤（T 分期）的增加而降低。GAS5 过表达抑制肿瘤细胞增殖和迁移，而用 PI3K 激活剂处理则降低了这种抑制作用。GAS5 过表达降低了食管癌细胞中 PI3K 的表达水平以及 Akt 和 mTOR 的磷酸化水平，而 PI3K 激活剂处理对 GAS5 表达没有明显影响。
与健康对照组相比，食管癌患者的 GAS5 下调，GAS5 过表达通过使 PI3K/AKT/mTOR 通路失活来抑制食管癌细胞的增殖和迁移。
