microRNA-503 inhibits gastric cancer cell growth and epithelial-to-mesenchymal transition.

microRNA-503 inhibits gastric cancer cell growth and epithelial-to-mesenchymal transition.
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DOI:
10.3892/ol.2014.1868
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发表时间:
2014-04
期刊:
影响因子:
2.9
通讯作者:
Wu XL
Wu XL
中科院分区:
医学4区
文献类型:
--
作者:
Peng Y;Liu YM;Li LC;Wang LL;Wu XL

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上皮间质转化(EMT)被认为与癌细胞恶性程度有关,也是导致癌症侵袭和转移的原因。最近的证据表明,小的非蛋白质编码RNA [microRNA(miRNAs/miRs)]可能是EMT的强大调节因子。本研究旨在系统研究miR-503在胃癌组织中的表达,并分析miR-503在胃癌EMT中的作用。本研究采用定量聚合酶链反应(PCR)方法检测胃癌细胞株和胃癌组织中miR-503的表达。用Transwell法、MTT法和克隆形成实验分析胃癌细胞的迁移、侵袭和增殖能力。在miR-503转染后,通过免疫印迹分析检测间充质标志物的表达,包括纤连蛋白、波形蛋白、N-钙粘蛋白、SNAIL和上皮标志物E-钙粘蛋白。发现miR-503在胃癌细胞系中的表达与正常胃粘膜细胞系相比降低,并且miR-503在非转移来源的胃癌细胞系中的表达与转移来源的细胞系相比上调。肿瘤组织中miR-503的表达水平显著低于癌旁正常粘膜组织,且有转移的患者中miR-503的表达水平显著低于无转移的患者。miR-503抑制胃癌细胞的迁移、侵袭和增殖。在用miR-503转染的AGS细胞系中,纤连蛋白、波形蛋白、N-钙粘蛋白和SNAIL蛋白水平降低,但E-钙粘蛋白表达增加。综上所述,本研究结果表明,miR-503作为一种新的胃癌肿瘤抑制基因,可以抑制胃癌细胞中的EMT。
Epithelial-to-mesenchymal transition (EMT) is believed to be associated with cancer cell malignancy, and also to cause cancer invasion and metastasis. Recent evidence indicates that small non-protein coding RNA [microRNAs (miRNAs/miRs)] may act as powerful regulators of EMT. The present study aimed to systematically delineate miR-503 expression in gastric cancer and analyse the function of miR-503 in gastric cancer EMT. In the present study, miR-503 expression was detected in gastric cancer cell lines and gastric cancer tissues by quantitative polymerase chain reaction. Gastric cancer cell migration, invasion and proliferation capabilities were analysed by Transwell, MTT and clonability assays. The expression of mesenchymal markers, including fibronectin, vimentin, N-cadherin, SNAIL and the epithelial marker, E-cadherin, was examined by immunoblot analysis following miR-503 transfection. miR-503 expression was found to be reduced in gastric cancer cell lines compared with normal gastric mucosa cell lines, and the expression of miR-503 was upregulated in non-metastatic-derived gastric cancer cell lines compared with metastatic-derived lines. miR-503 expression levels were significantly reduced in tumour tissues in comparison with adjacent normal mucosa tissues, and the miR-503 expression levels in patients with metastases were significantly lower than those in patients without. miR-503 inhibited gastric cancer cell migration, invasion and proliferation. Fibronectin, vimentin, N-cadherin and SNAIL protein levels were decreased, but E-cadherin expression was increased in an AGS cell line transfected with miR-503. Taken together, the present findings indicate that miR-503 acts as a novel tumour suppressor gene in gastric cancer and can inhibit EMT in gastric cancer cells.
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