The ubiquitous
mRNA binding protein human
antigen R (HuR), a member of the embryonal lethal abnormal vision
protein family has a critical impact on the post-transcriptional control of AU-rich element bearing
mRNA regulons implied in
inflammation, senescence, and
carcinogenesis. HuR in addition to mRNA stability can affect many other aspects of
mRNA processing including splicing, polyadenylation, translation, modulation of
miRNA repression, and intracellular
mRNA trafficking. Since many of the identified HuR
mRNA targets ("HuR
mRNA regulons") encode
tumor-related
proteins, HuR is not only discussed as an useful
biomarker but also as promising therapeutic target for treatment of various human
cancers. HuR which is most abundantly localized in the nucleus is translocated to the cytoplasm which is fundamental for most of the described HuR functions on target mRNAs. Accordingly, an elevation in cytoplasmic HuR was found in many
tumors and correlated with a high grade of
malignancy and a poor prognosis of patients. Therefore, direct interference with the intracellular trafficking of HuR offers an attractive approach to intervene with pathologically deregulated HuR functions. Data from several laboratories implicate that the integrity of the cytoskeleton is critical for HuR-mediated intracellular
mRNA localization and translation. This review will particularly focus on drugs which have proven a direct inhibitory effect on HuR translocation. Based on the results from those studies, we will also discuss on the principle value of targeting cytoskeleton-dependent transport of HuR by natural or synthetic inhibitors as a potential therapeutic avenue for interfering with dysregulated post-transcriptional HuR
mRNA regulons and related
tumor cell functions. In spite of that, interfering with cytoplasmic HuR transport could highlight a so far underestimated action of microtubule inhibitors clinically used for
cancer chemotherapy.