In recent years, miRNAs were established to be essential in normal and pathological development and function of cardiovascular system. Interacting with various target genes, these molecules act as multifunctional regulators of various intracellular signaling pathways. MicroRNA-375 was shown to be involved in development of many cardiovascular diseases. The precise mechanisms and effects of its regulatory action are still unclear.

OBJECTIVE

To evaluate the effect of miR-375 overexpression on expression of genes associated with cardiovascular diseases.

MATERIAL AND METHODS

To assess the effect of miR-375 overexpression on gene expression, we transfected HUVEC cells with miR-375 mimic and control oligonucleotide not complementary to known human RNAs. After that, transcriptional profiling by high-throughput RNA sequencing was performed. Proliferative activity and apoptosis of transfected cells were assessed using the MTT assay and flow cytometry after double staining with FITC-labeled Annexin V and propidium iodide.

RESULTS. A

Nalysis of transcriptional profiles showed that miR-375 overexpression in HUVEC cells led to dynamic changes in expression of certain genes including gene CXCL8 encoding interleukin-8 and miR-596. The common targets for miR-375 and miR-596 were the MCL1, WWC2, CNBP and SOX4 genes.

CONCLUSION

MicroRNA-375 overexpression in HUVEC cells leads to dynamic changes in the transcriptome. The most promising candidates for further study of miR-375 regulatory role in endothelial cells are the CXCL8 and WWC2 genes. Indeed, their products are involved in development of cardiovascular system and pathogenesis of cardiovascular diseases. The gene of miR-596 is also interesting in this regard.