MicroRNA-375 inhibits the proliferation, migration and invasion of kidney cancer cells by triggering apoptosis and modulation of PDK1 expression

In this study we investigated the potential of miR-375 as the therapeutic target for the treatment of Kidney cancer. The results revealed that miR-375 is significantly downregulated in the Kidney cancer cells. To investigate the role therapeutic potential of miR-375, one kidney cancer cell line (A-498) was selected for further experimentation. It was observed that overexpression of miR-375 inhibits A-498 kidney cancer proliferation by induction of apoptosis. In addition, overexpression of miR-375 causes suppression of migration and invasion of the A-498 kidney cancers cells. Bioinformatic analysis revealed PDK1 to be putative target of miR-375 in Kidney cancer cells. The western blot analysis revealed the expression of PDK1 to be significantly upregulated in Kidney cancer cells and overexpression of miR-375 in A-498 cells caused inhibition of PDK1 preventing the phosphorylation of AKT (Thr308 and Ser473). Additionally, inhibition of PDK1 had similar effects as that of miR-375 overexpression on cell proliferation of A-498 kidney cancer cells. The inhibition of miR-375 expression could not rescue the effects of PDK-1 suppression on A-498 cell proliferation. In contrary, overexpression of PKD1 in A-498 cells transfected with miR-375 mimics could nullify the effects of miR-375 on proliferation of the A-498 cells. Taken together, we conclude that miR-375 regulates cell proliferation, migration and invasion of A-498 kidney cancer cells and may prove to be an important therapeutic t...
Source: Environmental Toxicology and Pharmacology - Category: Environmental Health Source Type: research