Chen Weidong, Tang Zhaoqing, Sun Yihong, Zhang Youyou, Wang Xuefei, Shen Zhenbin, Liu Fenglin, Qin Xinyu
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai;
Exp Ther Med. 2012 Feb;3(2):351-356. doi: 10.3892/etm.2011.411. Epub 2011 Dec 6.
The aim of this study was to identify and evaluate microRNAs (miRNAs) in gastric cancer lymph node metastasis. A miRNA array was used to compare the expression of miRNAs in primary gastric cancer and paired lymph node metastases. miRNAs found to be differentially expressed were validated in a cohort of primary gastric cancer tissues, and the relationship between expression and the clinicopathological characteristics of the specimens was analyzed. The expression level of miR-10a in a gastric mucosal cell line and three gastric cancer cell lines was also detected using qPCR. Moreover, the target genes for miR-10a were predicted using bioinformatic methods. Based on the results, four differentially expressed miRNAs were detected by the miRNA array. Compared with primary gastric cancer, lymph node metastases displayed downregulated expression of miR-24-1(*), miR-510 and miR-1284, while the expression of miR-10a was upregulated. Consequently, analysis found that the expression of miR-10a was associated with lymph node metastasis (P=0.047), but was independent of the state of lymphatic invasion (P=0.169) in the cohort of primary gastric carcinoma. The expression of miR-10a was at least 10-fold higher in the three gastric cancer cell lines than in the gastric mucosal cell line. Two gastric cancer cell lines, which were established from lymph node metastasis, expressed higher miR-10a compared to the primary tumor origin cell line. Bioinformatic analysis demonstrated that the target genes of miR-10a are involved in multiple related pathways of tumorigenesis and metastasis. In conclusion, our study suggests that miR-10a is involved in the development of gastric cancer and lymph node metastasis, particularly in the latter process.
本研究旨在鉴定和评估胃癌淋巴结转移中的微小RNA(miRNA)。使用miRNA芯片比较原发性胃癌及其配对淋巴结转移灶中miRNA的表达情况。在一组原发性胃癌组织中验证了差异表达的miRNA,并分析了其表达与标本临床病理特征之间的关系。还使用定量聚合酶链反应(qPCR)检测了胃黏膜细胞系和三种胃癌细胞系中miR-10a的表达水平。此外,利用生物信息学方法预测了miR-10a的靶基因。结果显示,miRNA芯片检测到四个差异表达的miRNA。与原发性胃癌相比,淋巴结转移灶中miR-24-1(*)、miR-510和miR-1284的表达下调,而miR-10a的表达上调。因此,分析发现,在原发性胃癌队列中,miR-10a的表达与淋巴结转移相关(P=0.047),但与淋巴管侵犯状态无关(P=0.169)。三种胃癌细胞系中miR-10a的表达比胃黏膜细胞系至少高10倍。由淋巴结转移建立的两种胃癌细胞系与原发性肿瘤来源细胞系相比,miR-10a表达更高。生物信息学分析表明,miR-10a的靶基因参与了肿瘤发生和转移的多个相关途径。总之,我们的研究表明,miR-10a参与了胃癌的发生发展及淋巴结转移,尤其是在后者过程中。