miR-519 suppresses tumor growth by reducing HuR levels

Abstract

The RNA-binding protein HuR is highly abundant in many cancers. HuR expression was recently found to be repressed by microRNA miR-519, which potently lowered HuR translation without influencing HuR mRNA abundance. Here, we examined the levels of HuR and miR-519 in pairs of cancer and adjacent healthy tissues from ovary, lung and kidney. In the three sample collections, the cancer specimens showed dramatically higher HuR levels, unchanged HuR mRNA concentrations, and markedly reduced miR-519 levels, when compared with healthy tissues. As tested using human cervical carcinoma cells, miR-519 reduced tumorigenesis in athymic mice. Compared with the tumors arising from control cells, cells overexpressing miR-519 formed significantly smaller tumors, while cells expressing reduced miR-519 levels gave rise to substantially larger tumors. Evidence that the miR-519-elicited reduction of huR was critical for its tumor suppressor influence was obtained by reducing HuR, as HuR-silenced cells formed markedly smaller tumors and were unable to form large tumors even after lowering miR-519 abundance. Together, our data reveal that miR-519 inhibits tumorigenesis in large part by repressing HuR expression. © 2010 Landes Bioscience.