Expression of HuR is associated with increased cyclooxygenase-2 expression in uterine cervical carcinoma.

The human family embryonic-lethal abnormal vision-like protein Hu antigen R (HuR) serves as a messenger RNA (mRNA)-binding protein and stabilizes a certain group of cellular mRNAs that contain adenylate/uridylate-rich elements in their 3-untranslated region. The HuR is predominantly located in the nucleus, but it shuttles between the nucleus and the cytoplasm. In the cytoplasm, it can stabilize certain transcripts. Reportedly, the mRNA of cyclooxygenase-2 (COX-2) can be stabilized by HuR in breast, ovary, colon, stomach, lung, and brain cancers. We investigated the expression of HuR and COX-2 in 308 primary uterine cervical carcinomas using immunohistochemistry. Nuclear HuR expression was seen in 280 (90.9%) of the cases, and cytoplasmic HuR expression was observed in 61 (19.8%) of the cases. The expression of nuclear HuR was significantly associated with stage (P = 0.031). We found that 135 patients (43.8%) showed positive reaction for the COX-2 protein. In the COX-2 positive cases, nuclear HuR expression was higher, but the difference was not statistically significant. Cytoplasmic HuR expression was significantly associated with tumor size (P = 0.029), stage (P = 0.005), and lymphatic/vascular invasion (P < 0.001). Considering only squamous cell lesions (carcinoma in situ, microinvasive squamous cell carcinoma [SCC], and invasive SCC), the cytoplasmic expression of HuR significantly increased in invasive SCC compared with microinvasive SCC or carcinoma in situ (P = 0.005). Cytoplasm HuR expression correlated with COX-2 (P < 0.001). There was no significant correlation between HuR (nuclear or cytoplasmic) expression and patient survival. Our results suggest that the cytoplasmic overexpression of HuR is associated with uterine cervical carcinomas with aggressive clinicopathologic features and that HuR might contribute to the stabilization of COX-2 mRNA in some uterine cervical carcinomas.