Computational analysis of miRNA mediated KDR gene regulation and natural VEGFR2 inhibitors from Persicaria hydropiper in hepatocellular carcinoma.

Liver cancer is one of the deadliest cancers worldwide. There is a growing need for natural therapeutic options due to the rising global morbidity incidence of liver cancer. Due to its crucial function in angiogenesis, vascular endothelial growth factor (VEGF) signaling is considered as an ideal target for therapeutic intervention. In this in silico study, we have screened 16 microRNAs (miRNAs) that target the KDR gene, which encode VEGFR-2, and 113 natural compounds derived from Persicaria hydropiper for their anti-angiogenic properties. MicroRNA, hsa-miR-17-3p was identified with potentials of downregulating KDR gene, using several in silico tools. Two possible compounds- 6-Hydroxyluteolin and Isorhamnetin were also identified after performing ADMET profiling and molecular docking. Furthermore, 100 ns molecular dynamics simulations were run to evaluate the stability and conformational changes of protein-ligand complexes. This study identified one microRNA and two natural compounds that showed strong interaction with KDR and its encoded VEGFR-2 receptor, respectively. To validate their effectiveness as therapeutic agents against hepatocellular carcinoma, additional wet lab studies using in vitro and in vivo techniques are necessary.