miRNA expression profile in primary gastric cancers and paired lymph node metastases indicates that miR-10a plays a role in metastasis from primary gastric cancer to lymph nodes

Abstract

Abstract. 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. IntroductionGastric cancer is one of the most common malignant tumors of the digestive system, and its early diagnosis rate is still low in China, where gastric cancer is typically diagnosed at a more advanced stage; metastasis is typically present at the time of diagnosis. However, conventional strategies based on radical surgery for the treatment of gastric cancer are not yet satisfactory. Therefore, investigation of the mechanisms of metastasis and recurrence of gastric cancer, and exploration of the methods for the effective prediction, prevention and treatment of tumor metastasis are attracting increased attention in both basic and clinical cancer research. microRNAs (miRNAs), discovered in 1993, are a class of non-coding RNAs 19-25 nt in length that regulate gene expression at the post-transcriptional level (1,2). These miRNAs regulate complicated cellular processes such as differentiation, proliferation and apoptosis (3) and are widely involved in tumorigenesis, tumor progression and metastasis (4,5). Recent research suggests that miRNAs are involved in tumor invasion and metastasis, in the context of breast cancer, colorectal cancer, esophageal squamous cell carcinoma, and pancreatic endocrine tumors (6,7). Few studies have reported the role of miRNAs in gastric cancer owing to ...

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