Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, Xi-Cheng District, Beijing, P.R. China.
Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8248-8256. doi: 10.26355/eurrev_201812_16519.
Circular RNAs (circRNAs) have recently shown capabilities as gene regulators in mammals. In this study, we aimed to evaluate the effects and mechanism of circ_0009910 in gastric cancer (GC).
Circ_0009910 expression was quantified by Real-time PCR in human GC cell lines and tissues. Association between circ_0009910 levels and clinicopathological factors and patient's prognosis was analyzed. The roles of circ_0009910 in regulating GC cell proliferation, colony formation, migration, and invasion were evaluated in vitro. Western blot analysis was conducted to detect the expressions of molecular markers of epithelial-mesenchymal transition (EMT).
Circ_0009910 expression level was elevated in GC tissues and cell lines and associated with clinical stage (p = 0.032), distant metastasis (p = 0.028) and differentiation (p = 0.007). Kaplan-Meier survival analysis indicated that circ_0009910 expression in positive group has a worse overall survival compared to the negative group (p = 0.0013). Multivariate analysis showed that circ_0009910 was an independent risk factor for GC (HR = 2.346, 95% CI: 1.673-3.775, p = 0.006). Knockdown of circ_0009910 expression can suppress BGC823 and AGS cells proliferation, migration and invasion in vitro experiments. The results of Western blot indicated that knockdown of circ_0009910 increased expression of E-cadherin and decreased expression of the mesenchymal markers, snail and N-cadherin.
Altogether, we demonstrate that circ_0009910 acts as a prognostic biomarker and promote cell proliferation, migration, invasion and EMT in GC, indicating that circ_0009910 may be a novel potential biomarker and therapeutic target of GC.
环状 RNA(circRNAs)最近在哺乳动物中表现出作为基因调节剂的能力。在这项研究中,我们旨在评估 circ_0009910 在胃癌(GC)中的作用和机制。
通过实时 PCR 定量检测人 GC 细胞系和组织中的 circ_0009910 表达。分析 circ_0009910 水平与临床病理因素和患者预后的关系。体外评估 circ_0009910 对 GC 细胞增殖、集落形成、迁移和侵袭的调节作用。通过 Western blot 分析检测上皮-间充质转化(EMT)分子标志物的表达。
circ_0009910 在 GC 组织和细胞系中的表达水平升高,与临床分期(p=0.032)、远处转移(p=0.028)和分化(p=0.007)相关。Kaplan-Meier 生存分析表明,阳性组的 circ_0009910 表达与阴性组相比,总生存期更差(p=0.0013)。多因素分析表明,circ_0009910 是 GC 的独立危险因素(HR=2.346,95%CI:1.673-3.775,p=0.006)。体外实验中,circ_0009910 表达的敲低可抑制 BGC823 和 AGS 细胞的增殖、迁移和侵袭。Western blot 结果表明,circ_0009910 表达的敲低增加了 E-钙粘蛋白的表达,降低了间充质标志物 snail 和 N-钙粘蛋白的表达。
总之,我们证明 circ_0009910 作为一种预后生物标志物,促进 GC 中的细胞增殖、迁移、侵袭和 EMT,表明 circ_0009910 可能是 GC 的一种新的潜在生物标志物和治疗靶点。