Clinical significance of HuR expression in human malignancy

Abstract

Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of target mRNAs. The aim of the present review was to summarize and present the currently available information in the English literature on HuR expression in various human tumors, verifying its possible clinical significance. HuR function is directly linked to its subcellular localization. In normal cells, HuR is mostly localized in the nucleus, while in malignant cells, an increase in cytoplasmic HuR levels has been noted, in both cell lines and tissue samples. Moreover, in malignancy, elevated HuR expression levels and cytoplasmic immunohistochemical pattern have been correlated with advanced clinicopathological parameters and altered expression levels of proteins implicated in neoplasia. Additionally, elevated HuR expression levels and mainly cytoplasmic immunohistochemical pattern were correlated with decreased patients' survival rate in various human tumors. HuR is a putative drug target for cancer therapy, since it is expressed ubiquitously in malignant clinical samples and has an apparently consistent role in tumor formation and progression.

Elevated Hu-Antigen Receptor (HuR) Expression is Associated with Tumor Aggressiveness and Poor Prognosis but not with COX-2 Expression in Invasive Breast Carcinoma Patients

“…ER-targeted endocrine therapies are effective for the treatment of patients with ER-positive breast tumors and tamoxifen is the most widely used endocrine anti-estrogen treatment. Interestingly, a number of studies has implicated HuR in ER and HER2 expression regulation and tamoxifen resistance, suggesting that HuR may play a crucial role in breast cancer development and possibly treatment, as recently reviewed by our group [15].…”

“…A gradually increasing number of studies have currently documented that HuR overexpression and cytoplasmic localization are associated with crucial clinicopathological parameters for patients' management and prognosis in several types of human malignancy, as recently reviewed by our group [15]. Moreover, a number of clinical studies in breast cancer patients have demonstrated that elevated HuR expression was correlated with crucial clinicopathological parameters and patients' survival, indicating that high HuR expression levels may constitute an aggravating factor for tumor growth and metastasis [15].…”

“…Moreover, a number of clinical studies in breast cancer patients have demonstrated that elevated HuR expression was correlated with crucial clinicopathological parameters and patients' survival, indicating that high HuR expression levels may constitute an aggravating factor for tumor growth and metastasis [15]. However, as far as concern breast carcinoma, opposite data also exist, supporting the notion that low HuR expression levels are associated with tumor aggressiveness and poor prognosis [15]. Moreover, a lot of currently available data supported substantial evidence that COX-2 is associated with the promotion of carcinogenesis and tumor cell resistance to apoptosis [10,11].…”

“…The most comprehensive studies so far have supported substantial evidence that HuR is implicated in several pathological conditions, such as atherosclerosis [16], tissue ischemia [17], pathologic inflammation [6] and neoplasia [15,18,19]. Notably, HuR has been suggested to participate in malignant transformation process by controlling cancerrelevant genes related with angiogenesis, differentiation, cell cycle, apoptosis, inflammatory response and cell signaling [15,[18][19][20][21].…”

“…Notably, HuR has been suggested to participate in malignant transformation process by controlling cancerrelevant genes related with angiogenesis, differentiation, cell cycle, apoptosis, inflammatory response and cell signaling [15,[18][19][20][21]. Moreover, HuR appears to exert a critical role in tumor formation, growth and metastasis by binding to mRNA encoding proteins and by affecting their expression via mRNA stabilization and/or altered translation [15,20,21]. Enhanced HuR expression and cytoplasmic localization have been associated with malignant phenotype and poor patients' prognosis in several human malignancies [18,22].…”