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环状 RNA 0009910 调控胃癌的生长和转移,并与不良预后相关。

Circ_0009910 regulates growth and metastasis and is associated with poor prognosis in gastric cancer.

机构信息

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.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8248-8256. doi: 10.26355/eurrev_201812_16519.

Abstract

OBJECTIVE

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).

PATIENTS AND METHODS

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).

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

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。

方法

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。

结果

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。

结论

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。

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