The Screening And The Biological Role Of MiRNAs In Gastric Cancer

Objective:To screen and identify the miRNAs related to gastric cancer. And clarify the role of miRNA in gastric cancer. Provide some novel ideas and rationales for the study and treatment of gastric cancer. Meanwhile, the miRNA we found can be a new biomarker specific to gastric cancer which can be used for the diagnosis and prognosis of gastric cancer.Methods:To investigate the different expression of the miRNAs in2pairs of gastric cancer tissues compared to adjacent normal tissues using gene microarray of Agilent human miRNA (8*60K) V18.0. To verify this screened results in56gastric cancer tissues using Real-time PCR. And then analyse the relationship between the miRNA and clinical data (age, gender, tumor size, TNM and lymph node metastasis). To examine the expression of miRNAs in7gastric cancer cell lines with different differentiated grades and gastric mucosa cells and then illustrate the role of miRNAs in gastric cancer.Results:1.30miRNAs were selected by miRNA array, the expression of14miRNAs were up-regulated and16miRNAs down-regulated in gastric cancer.2. Among the56gastric cancer tissues,10of the14miRNAs with high expression still had high expression in these tissues, and12of16miRNAs with low expression still had low expression in these tissues. Another8miRNAs expression were not related to gastric cancer.3.4miRNAs (miR-551b-3p, miR-100-5p, miR-363-3p and miR-215) were closely related to differentiated grades, TNM stages and lymph node metastasis of gastric cancer.4. The expression of miR-200a-3p was much higher in male gastric cancer tissues than in female samples.5. The gastric cancer tissues from patients who were more than50years had higher level of the miR-429expression than in patients less than50years.6. The expressions of miR-551b-3p, miR-100-5p and miR-363-3p were down-regulated significantly in gastric cancer cells compared to gastric mucosa cells. The lower expression of these miRNAs, the higher level of malignancy.7. The expression of miR-215was higher in gastric cancer cells than in gastric mucosa GES-1cells. There were no correlation found between the miRNAs expression and differentiated grades of gastric cancer.Conclusions:1. Many miRNAs have differential expression in gastric cancer tissues and cells which hint us the role of miRNAs is really important in the progress of gastric cancer.2. The expressions of miR-551b-3p, miR-100-5p and miR-363-3p were down-regulated significantly in gastric cancer tissues and cells. These expressions were closely related to differentiated grades, TNM stages and lymph node metastasis of gastric cancer. This revealed that miRNAs could effect the development of gastric cancer as a tumor-suppresser.3. The expression of miR-215was up-regulated dramatically in gastric cancer tissues and cells, which had close relationship with differentiated grades, TNM stages and lymph node metastasis of gastric cancer. This means miR-215may act as an oncogene.4. The abnormal expression of miR-200a-3p is related to gender of gastric cancer patients.5. The abnormal expression of miR-429is related to age of gastric cancer patients.6. We found that miR-551b-3p and miR-363-3p could be really important genes in the development of gastric cancer.7. The very much high expression of miR-215in gastric cancer implied that miR-215can be a biomarker for the diagnosis of gastric cancer.