Role of HuR in keratinocyte migration and wound healing

Human antigen R (HuR) is a post-translational modifier of mRNAs rich in AU- and U-rich elements. These mRNAs typically code for proteins involved in cell growth and differentiation, signal transduction, transcriptional and translational control, apoptosis, nutrient transport and metabolism. Thus, HuR affects a variety of biological functions and processes. Via its effect on growth and cellular migration, HuR has been shown to enhance clinical progression of a number of cancers. Its role in wound healing remains unknown. In the present study, we evaluated HuR tissue expression in a cohort of chronic healed and non-healed leg ulcers. We also evaluated the effect of HuR knockdown on a number of cellular processes using the HaCaT human keratinocyte cell line. HuR was expressed in greater levels in the 'chronic healed' cohort of ulcers, compared to the 'chronic non-healed', although this failed to reach statistical significance (p=0.13). HuR knockdown resulted in greater cellular growth, faster progression through the cell cycle and reduced apoptosis. Furthermore, it reduced cellular adhesion rates without affecting migration. We, therefore, concluded that HuR promotes wound healing, primarily through its effect on cellular adhesion. It also slows cellular growth rate via its effect on both cell cycle progression and rates of apoptosis.