HuR as a molecular target for cancer therapeutics and immune-related disorders

Abstract

The control of eukaryotic gene expression occurs at multiple levels, from transcription to messenger RNA processing, transport, localization, turnover, and translation. RNA-binding proteins control gene expression and are involved in different stages of mRNA processing, including splicing, maturation, turnover, and translation. A ubiquitously expressed RBP Human antigen R is engaged in the RNA processes mentioned above but, most importantly, controls mRNA stability and turnover. Dysregulation of HuR is linked to many diseases, including cancer and other immune-related disorders. HuR targets mRNAs containing AU-rich elements at their 3'untranslated region, which encodes proteins involved in cell growth, proliferation, tumor formation, angiogenesis, immune evasion, inflammation, invasion, and metastasis. HuR overexpression has been reported in many tumor types, which led to a poor prognosis for patients. Hence, HuR is considered an appealing drug target for cancer treatment. Therefore, multiple attempts have been made to identify small molecule inhibitors for blocking HuR functions. This article reviews the current prospects of drugs that target HuR in numerous cancer types, their mode of action, and off-target effects. Furthermore, we will summarize drugs that interfered with HuR-RNA interactions and established themselves as novel therapeutics. We will also highlight the significance of HuR overexpression in multiple cancers and discuss its role in immune functions. This review provides evidence of a new era of HuR-targeted small molecules that can be used for cancer therapeutics either as a monotherapy or in combination with other cancer treatment modalities.

Keywords: Cancer growth and progression and small-molecule inhibitors; Posttranscriptional gene regulation; RNA-binding proteins; mRNA translation; mRNA turnover.