The Role of DND1 in Cancers

• Published in: Cancers Vol. 13; no. 15; p. 3679
• Main Authors: Zhang, Yun, Godavarthi, Jyotsna D, Williams-Villalobo, Abie, Polk, Shahrazad, Matin, Angabin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.07.2021; MDPI
• Subjects: 3' Untranslated regions; Apoptosis; Cancer; Cell cycle; Cyclin-dependent kinases; Genes; Genomes; Kinases; MicroRNAs; miRNA; mRNA; Mutation; Nonsense mutation; Ovaries; Progenitor cells; Proteins; Review; RNA-binding protein; Stem cells; Stop codon; Testes; Translation; Translation initiation; Tumor cell lines; Tumors; teratomas; translation regulator; somatic cancers; germ cell; DND1
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers13153679

The mutation in Dead-End 1 ( ), , which leads to a premature stop codon, has been determined to be the cause for primordial germ cell deficiency, accompanied with a high incidence of congenital testicular germ cell tumors (TGCTs) or teratomas in the 129/Sv- mice. As an RNA-binding protein, DND1 can bind the 3'-untranslated region (3'-UTR) of mRNAs and function in translational regulation. DND1 can block microRNA (miRNA) access to the 3'-UTR of target mRNAs, thus inhibiting miRNA-mediated mRNA degradation and up-regulating translation or can also function to degrade or repress mRNAs. Other mechanisms of DND1 activity include promoting translation initiation and modifying target protein activity. Although mutation causes spontaneous TGCT only in male 129 mice, it can also cause ovarian teratomas in mice when combined with other genetic defects or cause germ cell teratomas in both genders in the WKY/Ztm rat strain. Furthermore, studies on human cell lines, patient cancer tissues, and the use of human cancer genome analysis indicate that DND1 may possess either tumor-suppressive or -promoting functions in a variety of somatic cancers. Here we review the involvement of DND1 in cancers, including what appears to be its emerging role in somatic cancers.