Unveiling the role of RAI14 in cancer: Biological significance and translational perspectives

Retinoic acid-induced protein 14 (RAI14) is an actin-binding protein that regulates actin dynamics, cell adhesion, and migration. RAI14 dysregulation has been reported to facilitate the development of at least 10 tumor types based on the findings from over 20 original research articles. This review article aims to fill in the gap in the literature by providing a comprehensive summary of the putative tumor-regulatory roles of RAI14 in different cancers. Overall, RAI14 can affect protein kinase B (AKT), mammalian target of rapamycin, yes-associated protein/Hippo, apoptosis, and epithelial-to-mesenchymal transition activities to promote tumorigenesis. Several noncoding RNAs like miR-23b-3p and AFAP1-AS1 can directly or indirectly affect RAI14 expression to control its tumor-modulatory function epigenetically. Additionally, RAI14 tissue or serum level are overexpressed in at least seven human tumors, including breast, gastrointestinal, genitourinary, and brain cancers. This gives RAI14 the translational potential as a diagnostic or prognostic biomarker. Targeting RAI14 as a cancer antigen can also potentially help halt tumor progression. Future large-scale trials are needed to confirm the tumor-regulatory role of RAI14 in human cancer and to evaluate the sensitivity, reliability, and accuracy of using this target as a biomarker or therapeutic target.