miR-195 mimic, a new therapeutic strategy for suppressing CDK6 expression and progression of hepatocellular...

Hepatocellular carcinoma (HCC), a leading cause of death worldwide, is primarily caused by uncontrolled cellular proliferation, invasion and metastasis leading to tumor development in the liver. miR-195 regulates G1 to S phase transition in the cell cycle by targeting CDK6. In the current study, expression of miR-195 was significantly reduced while that of CDK6 was upregulated in HCC patients. The results of expression analysis were supported by the Pearson correlation coefficient indicating a moderate negative (r = -0.459, p = 0.02) relation between miR-195 and CDK6. However, the association of miR-195 and CDK6 with age and sex was not statistically significant. The predicted secondary and tertiary structures of miR-195 showed the presence of loops, stems, and flanking regions. Further, in silico analysis identified potential amino acid residues in CDK6, CDK4 and Cyclin D1 proteins interacting with the miR-195. We designed a mimic RNA of miR-195 by mutagenesis at 4 points. The mimic RNA_3 of miR-195 presented a well-defined stable structure showing strong binding interactions with CDK4 and Cyclin D1 and comparable interactions with CDK6. In conclusion, our study has demonstrated the potential of using miR-195 mimic RNA as a therapeutic strategy to target the CDK6 gene in HCC with reduced miR-195 expression.