Placenta Growth Factor Influences miR-483-5p, miR-483-3p, miR-4669 and miR-16-5p Expression in MKN-45-Derived Spheroid Body-Forming Cells

Placenta growth factor (PlGF) is a crucial player of the human gastric cancer development. PlGF signalling pathway affects the expression of genes involving in angiogenesis and metastasis. Studies have hinted association between abnormal intracellular signal transduction and miRNAs expression profile in cancer initiation and progression. Changes in the expression of miR-483-5p, miR-483-3p, miR-16-5p and miR-4669 are reported in the spheroid body (SB)-forming cells derived from gastric cancer cell line MKN-45. Given the importance of PlGF and also the expression change of the above mentioned miRNAs in gastric cancer, this study was designed to investigate the effect of siRNA-mediated knockdown of Plgf on the expression of these miRNAs in the MKN-45 derived SB-forming cells. In addition, bioinformatics analysis was performed on the miRNAs to predict their potential targets that associated with survival, apoptosis and angiogenesis processes. Results showed that with except miR-483-3p, which was down-regulated, another 3 miRNAs were significantly up-regulated in the Plgf-knockdown samples. Furthermore, the in silico analysis revealed that these miRNAs influence the expression of a set of genes, which are involved in various signal transduction pathways. Moreover, it showed that they affect cellular processes, including proliferation, apoptosis and angiogenesis. In conclusion, the current study reveals that down-regulation of Plgf influences the miRNAs expression in MKN-45 derived SB-forming cells. Moreover, our findings indicate that miR-483-5p, miR-483-3p and miR-16-5p can induce cancer initiation and progression through targeting genes involved in the cell cycle, apoptosis and angiogenesis processes.