Purpose: It is widely known that some specific microRNAs can regulate the expressions of genes in gastric cancer cells at the post-transcriptional level. Previous studies have identified that miRNA-4766-5p was involved in tumor cell proliferation and can be an independent prognostic indicator for malignant pleural mesothelioma. However, the mechanism underlying gastric cancer via the miRNA-4766-5p pathway remains to be blank.
Methods: We investigated the expression of miR-4766-5p in gastric cancer tissues and cells through qRT-PCR. We used RNAi to change the expressions of miR-4766-5p in gastric cancer cell lines, AGS and MKN45. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the mRNA expression of miR-4766-5p. We identified cell proliferation by CCK8 and clone formation assays. We analyzed the cell apoptosis and cycle through flow cytometry. At last, we used a dual-luciferase reporter assay to illustrate the interaction between miR-4766-5p and NKAP and used Western blot to determine the protein expression of signaling pathways.
Results: We found that 1) miR-4766-5p was down-regulated in gastric cancer tissues and cells lines; 2) miR-4766-5p inhibited cell proliferation of gastric cancer cell lines significantly; 3) miR-4766-5p significantly inhibited cell migration and invasion of gastric cancer cells; 4) miR-4766-5p induced gastric cancer cell apoptosis. 5) NKAP was a direct target gene of miR-4766-5p; and 6) miR-4766-5p induced inactivation of AKT/mTOR pathway.
Conclusion: The above results indicate that miR-4766-5p suppressed the proliferation and metastasis of gastric cancer cells through targeting NKAP. Our findings could probably contribute to the diagnostics and prognostics of gastric cancer through new methodologies.
Keywords: miR-4766-5p, progression, gastric cancer, NKAP