Effect and Mechanism of lncRNA FOXD2-AS1 on Proliferation, Invasion and Metastasis of Gastric Cancer Cells
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摘要:目的
探究lncRNA FOXD2-AS1对胃癌细胞增殖侵袭转移的影响及机制。
方法数据挖掘及临床样本验证lncRNA FOXD2-AS1在胃癌与癌旁组织中的表达情况、与患者临床病理分期及预后的相关性；在胃癌细胞系BGC-823中抑制lncRNA FOXD2-AS1的表达，采用CCK8比色法检测细胞增殖情况，采用细胞划痕和Transwell实验检测细胞迁移及侵袭情况；蛋白印迹实验检测上皮-间质转化相关蛋白E-Cadherin、N-cadherin、Vimentin的表达以及Wnt-β-catenin通路关键蛋白分子表达情况。
结果lncRNA FOXD2-AS1在胃癌组织中较癌旁组织明显增高，并与患者肿瘤分期及预后相关；lncRNA FOXD2-AS1在胃癌各细胞系中表达升高，抑制lncRNA FOXD2-AS1的表达明显降低胃癌细胞增殖、迁移及侵袭能力，并上调E-Cadherin的表达，下调N-cadherin、Vimentin、β-catenin及Cyclin-D1的表达（均P < 0.05）。
结论lncRNA FOXD2-AS1在胃癌组织中高表达，并通过Wnt-β-catenin通路调节EMT相关蛋白表达从而促进胃癌的发展，影响患者生存预后。
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关键词:
- 胃癌 /
- 长链非编码RNA /
- EMT /
- Wnt-β-catenin通路
Abstract:ObjectiveTo investigate the effect and mechanism of lncRNA FOXD2-AS1 on the proliferation, invasion and metastasis of gastric cancer cells.
MethodsData mining and clinical samples were used to verify the expression of lncRNA FOXD2-AS1 in cancer and adjacent normal tissues, and its correlation with clinical pathological stage and prognosis of the patients. The expression of lncRNA FOXD2-AS1 in gastric cancer cell line BGC-823 was inhibited. CCK8 colorimetric method, wound-healing assay and Transwell experiment were used to detect cell proliferation, migration and invasion. Western blot was used to detect the expression of E-Cadherin, N-cadherin, Vimentin and critical proteins of Wnt/β-catenin pathway.
ResultslncRNA FOXD2-AS1 expression was significantly higher in cancer tissues than that in adjacent tissues, and was associated with tumor stage and prognosis. The expression of lncRNA FOXD2-AS1 was increased in gastric cancer cell lines. Inhibition of lncRNA FOXD2-AS1 expression could significantly reduce the proliferation, migration and invasion of gastric cancer cells, and upregulate E-Cadherin expression while down-regulate the expression of N-cadherin, Vimentin, β-catenin and Cyclin-D1 (all P < 0.05).
ConclusionLncRNA FOXD2-AS1 is highly expressed in gastric cancer tissues, and regulates the expression of EMT-related proteins through the Wnt-β-catenin pathway to promote the development of gastric cancer and affect the prognosis of patients.
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Key words:
- Gastric cancer /
- lncRNA /
- EMT /
- Wnt-β-catenin pathway
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作者贡献袁正泰：研究设计、实施以及论文撰写王永恒：研究设计以及论文修改黄湘俊：研究设计、实施以及论文审核
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图 1 IncRNA FOXD2-AS1在胃癌组织中的表达及与患者预后的关系
Figure 1 lncRNA FOXD2-AS1 expression in gastric cancer tissues and its relation with patients' prognosis
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图 2 lncRNA FOXD2-AS1在不同胃癌细胞系中的表达
Figure 2 lncRNA FOXD2-AS1 expression in different gastric cancer cell lines
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图 3 lncRNA FOXD2-AS1沉默效率验证(A)、CCK8增殖实验(B)及细胞平板克隆形成实验(C)结果
Figure 3 Results of lncRNA FOXD2-AS1 silencing efficiency verification(A), CCK8 proliferation experiment (B) and cell plate clone formation experiment(C)
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图 4 划痕实验(A)和Transwell小室侵袭实验(B)结果
Figure 4 Results of wound healing assay(A) and Transwell test(B)
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图 5 沉默lncRNA FOXD2-AS1对Wnt/β-catenin通路相关蛋白及EMT相关蛋白qRT-PCR实验(A)和Western blot实验(B)验证结果
Figure 5 Effect of lncRNA FOXD2-AS1 silencing on expression of Wnt/β-catenin pathway related proteins and EMT-related proteins detected by qRT-PCR(A) and Western blot(B)
表 1 lncRNA FOXD2-AS1表达与胃癌患者临床病理分期相关性
Table 1 Correlation between lncRNA FOXD2-AS1 expression and clinicopathological stage of gastric cancer patients
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