Together, these findings indicate that miR-199a acts as a tumour suppressor and its downregulation in tumour tissues may contribute to the progression and metastasis of RCC through a mechanism involving ROCK1, suggesting miR-199a as a potential new diagnostic and therapeutic target for the treatment of RCC.
Using luciferase and western blot assays we identified that Rho-associated coiled coil-containing protein kinases 1 (ROCK1) was a direct target gene for miR-199a. miR-199a regulated proliferation, invasion, and apoptosis of clear cell renal cell carcinoma (ccRCC) cells by modulating ROCK1 expression.
Downregulation of ROCK1 by small interfering RNA (siRNA) selectively reduced the colony-forming ability of VHL-deficient CC-RCC, thus mimicking the effect of Y-27632 treatment, whereas downregulation of ROCK2 had no effect.
We found two SNPs (Cav-1 rs1049334 and ROCK1rs35996865) were significantly associated with the increasing risk of ccRCC (P = 0.002 and P < 0.001 respectively).