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长链非编码 RNA ZEB1-AS1 与胃癌预后不良相关,并促进癌细胞转移。

Long non-coding RNA ZEB1-AS1 is associated with poor prognosis in gastric cancer and promotes cancer cell metastasis.

机构信息

Department of Gastroenterology, Zhoukou Central Hospital, Zhoukou, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 May;22(9):2624-2630. doi: 10.26355/eurrev_201805_14956.

Abstract

OBJECTIVE

To investigate the expression of long non-coding RNA zinc-finger E-box binding homeobox 1-AS1 (lncRNA ZEB1-AS1) in gastric cancer cells and tissues, to study its effect on the gastric cancer cell metastasis capacity, and analyze its clinical significance.

PATIENTS AND METHODS

The relative expression level of lncRNA ZEB1-AS1 in gastric cancer cells was detected via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Transwell assay was used to detect the effects of lncRNA ZEB1-AS1 on the invasion and metastasis capacities of gastric cancer cells. qRT-PCR was used to detect the relative expression level of lncRNA ZEB1-AS1 in 75 pairs of gastric cancer tissues, and the correlations of its expression with the pathological characteristics and prognosis of patients were statistically analyzed.

RESULTS

qRT-PCR showed that compared with that in the normal gastric epithelial cell (GES-1), the expression level of lncRNA ZEB1-AS1 was up-regulated in gastric cancer cells (MKN28, MKN45, BGC823, MGC803, KATOIII, and SGC7901). LncRNA ZEB1-AS1 interfering sequence was transfected into model cells, and Transwell assay showed that the cell invasion and migration capacities were significantly inhibited. qRT-PCR also revealed that the expression of lncRNA ZEB1-AS1 was up-regulated in 55 out of 75 cases of gastric cancer and para-carcinoma tissues (fold change > 1). Statistical analysis showed that the high expression of lncRNA ZEB1-AS1 was positively correlated with TNM staging (p = 0.002), lymph node metastasis (p = 0.002), and invasion degree (p = 0.004). The survival time of patients with high expression of lncRNA ZEB1-AS1 in gastric cancer tissues was shorter than that of patients with low expression (p = 0.004).

CONCLUSIONS

LncRNA ZEB1-AS1 is highly expressed in gastric cancer tissues and cells, and it is expected to be a new prognostic marker of gastric cancer used for the clinical diagnosis and prognostic evaluation. After intervention in lncRNA ZEB1-AS1 expression, the cell invasion and migration are inhibited, and lncRNA ZEB1-AS1 may be an important target to reverse the malignant phenotype of gastric cancer.

摘要

目的

研究长链非编码 RNA 锌指 E 框结合同源盒 1-反义 RNA(lncRNA ZEB1-AS1)在胃癌细胞和组织中的表达,探讨其对胃癌细胞转移能力的影响,并分析其临床意义。

方法

采用实时荧光定量逆转录聚合酶链反应(qRT-PCR)检测胃癌细胞中 lncRNA ZEB1-AS1 的相对表达水平。Transwell 实验检测 lncRNA ZEB1-AS1 对胃癌细胞侵袭和转移能力的影响。采用 qRT-PCR 检测 75 对胃癌组织中 lncRNA ZEB1-AS1 的相对表达水平,并统计分析其表达与患者病理特征和预后的相关性。

结果

qRT-PCR 结果显示,与正常胃上皮细胞(GES-1)相比,胃癌细胞(MKN28、MKN45、BGC823、MGC803、KATOIII 和 SGC7901)中 lncRNA ZEB1-AS1 的表达水平上调。转染 lncRNA ZEB1-AS1 干扰序列后,Transwell 实验显示细胞侵袭和迁移能力明显受到抑制。qRT-PCR 还显示,75 例胃癌及癌旁组织中 55 例 lncRNA ZEB1-AS1 表达上调(倍数变化>1)。统计学分析显示,lncRNA ZEB1-AS1 高表达与 TNM 分期(p=0.002)、淋巴结转移(p=0.002)和浸润程度(p=0.004)呈正相关。胃癌组织中 lncRNA ZEB1-AS1 高表达患者的生存时间短于低表达患者(p=0.004)。

结论

lncRNA ZEB1-AS1 在胃癌组织和细胞中高表达,有望成为胃癌临床诊断和预后评估的新的预后标志物。干预 lncRNA ZEB1-AS1 表达后,细胞侵袭和迁移受到抑制,lncRNA ZEB1-AS1 可能是逆转胃癌恶性表型的重要靶点。

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