MicroRNAs, Tristetraprolin Family Members and HuR: A Complex Interplay Controlling Cancer-Related Processes

SIMPLE SUMMARY: AU-rich Element Binding Proteins (AUBPs) represent important post-transcriptional regulators of gene expression by regulating mRNA decay and/or translation. Importantly, AUBPs can interfere with microRNA-dependent regulation by (i) competing with the same binding sites on mRNA targets, (ii) sequestering miRNAs, thereby preventing their binding to their specific targets or (iii) promoting miRNA-dependent regulation. These data highlight a new paradigm where both miRNA and RNA binding proteins form a complex regulatory network involved in physiological and pathological processes. However, this interplay is still poorly considered, and our current models do not integrate this level of complexity, thus potentially giving misleading interpretations regarding the role of these regulators in human cancers. This review summarizes the current knowledge regarding the crosstalks existing between HuR, tristetraprolin family members and microRNA-dependent regulation. ABSTRACT: MicroRNAs represent the most characterized post-transcriptional regulators of gene expression. Their altered expression importantly contributes to the development of a wide range of metabolic and inflammatory diseases but also cancers. Accordingly, a myriad of studies has suggested novel therapeutic approaches aiming at inhibiting or restoring the expression of miRNAs in human diseases. However, the influence of other trans-acting factors, such as long-noncoding RNAs or RNA-Binding-Proteins, which compete, interfere, or cooperate with miRNAs-dependent functions, indicate that this regulatory mechanism is much more complex than initially thought, thus questioning the current models considering individuals regulators. In this review, we discuss the interplay existing between miRNAs and the AU-Rich Element Binding Proteins (AUBPs), HuR and tristetraprolin family members (TTP, BRF1 and BRF2), which importantly control the fate of mRNA and whose alterations have also been associated with the development of a wide range of chronic disorders and cancers. Deciphering the interplay between these proteins and miRNAs represents an important challenge to fully characterize the post-transcriptional regulation of pro-tumorigenic processes and design new and efficient therapeutic approaches.