The Role of the RNA-Binding Protein Family MEX-3 in Tumorigenesis

Abstract

The muscle excess 3 (MEX-3) protein was first identified in Caenorhabditis elegans (C. elegans), and its respective homologues were also observed in vertebrates, including humans. It is a RNA-binding protein (RBP) with an additional ubiquitin E3 ligase function, which further acts as a post-transcriptional repressor through unknown mechanisms. In humans, MEX-3 proteins post-transcriptionally regulate a number of biological processes, including tumor immunological relevant ones. These have been shown to be involved in various diseases, including tumor diseases of distinct origins. This review provides information on the expression and function of the human MEX-3 family in healthy tissues, as well after malignant transformation. Indeed, the MEX-3 expression was shown to be deregulated in several cancers and to affect tumor biological functions, including apoptosis regulation, antigen processing, and presentation, thereby, contributing to the immune evasion of tumor cells. Furthermore, current research suggests MEX-3 proteins as putative markers for prognosis and as novel targets for the anti-cancer treatment.

Oncogenic Potential of the Dual-Function Protein MEX3A

“…Therefore, they influence cell proliferation, migration, signaling pathways and potentially contribute to tumor immune escape (for review, see Ref. [ 34 ]).…”

“…In this context, MEX3 proteins, particularly MEX3B and C, could contribute to an immune evasion of tumors (for review, see Ref. [ 34 ]). In sum, these findings suggest a link between the RNA binding and E3 ligase activity, but if and how RNA binding influences E3 ligase activity and substrate recognition and to which extend this is associated with specific RNA interactions and the formation of ternary protein-RNA complexes remains to be unraveled.…”

“…Whereas MEX3A and B are predominantly expressed in reproductive tissues (e.g., testis, ovary, and endometrium), MEX3C and MEX3D exhibit low overall tissue specificity. Obvious discrepancies between reported protein and mRNA expression as well as publicly available data are discussed in [ 34 ].…”

“…Deregulated, mainly upregulated expression of MEX3A-C proteins has been reported in various cancer types (for review, see Ref. [34]); however, the most severe deregulation was observed for MEX3A and MEX3C. Consistently, analyses of, e.g., liver transcriptome data from the TCGA project (www.cancer.gov/tcga; accessed on 26 March 2021) (obtained via the GDC data portal; [55]) revealed a significant upregulation of MEX3 proteins (Figure 2c).…”

The viral nucleocapsid protein and the human RNA-binding protein Mex3A promote translation of the Andes orthohantavirus small mRNA

“…The biological significance of this observation remains unclear. However, the hMex3A has a crucial role in tumorigenesis and malignant progression [ 65 , 66 ]. Maybe the hMex3A-eIF4G interaction is essential for hMex3A’s oncogenic potential.…”