The enhancer of zeste homolog 2 (EZH2), a potential therapeutic target, is regulated by miR-101 in renal cancer cells

► EZH2 is overexpressed in the nuclei of renal cancer cells. ► Nuclear EZH2 is associated with advanced stage and worse survival of RCC patients. ► EZH2 is negatively regulated by miR-101 in renal cancer cells. ► Depletion of EZH2 leads to re-expression of p27Kip1. ► Reintroduction of miR-101 results in suppression of cell proliferation. We investigated a prognostic significance and the mechanism of aberrant nuclear expression of EZH2, a histone methyltransferase, in human renal cell carcinoma (RCC). We found nuclear EZH2 in 48 of 100 RCCs and it was significantly correlated with worse survival in RCC patients. We detected a decreased expression of miR-101 in 15 of 54 RCCs. We found that re-expression of miR-101 resulted in EZH2 depletion and decreased renal cancer cell proliferation. Our results show nuclear EZH2 as a prognostic marker of worse survival in human RCC, and identify miR-101 as a negative regulator of EZH2 expression and renal cancer cell proliferation.