Identification and characterization of tumor suppressor and oncogenic miRNAs in gastric cancer

摘要

The aim of the present study was to screen for and identify microRNAs (miRNAs/miRs) that are associated with gastric cancer and to clarify the role of these miRNAs in gastric cancer. Thus, the differential expression of a panel of miRNAs in two pairs of gastric cancer tissues and their matched adjacent healthy tissues was investigated by performing a microarray analysis. To verify the results of this screen, 56 gastric cancer tissues were analyzed for the selected miRNAs using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The association between the expression of a specific miRNA and the clinical data relating to the tissue samples [including age, gender, tumor size, tumor node metastasis (TNM) stage and lymph-node metastasis] were subsequently examined. A total of 31 differentially expressed miRNAs were identified in the miRNA array. Using RT-qPCR to verify these results, it was determined that 10 miRNAs exhibited high mRNA expression levels and 13 miRNAs exhibited a low expression in the gastric cancer tissue samples, while 8 miRNAs did not demonstrate an association with gastric cancer. Thus, the microarray and RT-qPCR results demonstrated 74.2% (23/31 miRNAs) agreement. The association between the 23 miRNAs and the clinicopathological characteristics of the gastric cancer samples was investigated. It was identified that the expression levels of miR-551b-3p, miR-133b, miR-100-5p and miR-363-3p were significantly downregulated in the gastric cancer tissues, and this downregulation was closely correlated with the degree of differentiation (i.e., tumor grade), TNM stage and lymph-node metastasis (P<0.05). By contrast, the expression of miR-215 was significantly upregulated in the gastric cancer tissues, and its expression level was correlated with tumor differentiation, TNM stage and lymph-node metastasis (P<0.05). Furthermore, miR-200a-3p was upregulated in the gastric cancer tissues and its expression was significantly more prevalent in male patients compared with female patients (P<0.05). miR-429 was upregulated in the gastric cancer tissues and its expression was significantly higher in patients who were >50 years of age (P<0.05). These data indicate that a number of these miRNAs may be important in the development of gastric cancer. In particular, miR-551b-3p, miR-133b, miR-100-5p and miR-363-3p may act as tumor suppressors in the development of gastric cancer. By contrast, miR-215 appears to exhibit oncogenic properties and promote the development of gastric cancer. In addition, the abnormal expression of miR-200a-3p may be associated with gender, while the abnormal expression of miR-429 may be associated with age in patients with gastric cancer. However, additional studies are required to delineate the underlying mechanisms of the association, and to explore their potential as valid biomarkers in the diagnosis, classification and prognosis of gastric cancer.