Zhang Yun, Godavarthi Jyotsna D, Williams-Villalobo Abie, Polk Shahrazad, Matin Angabin
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA.
Cancers (Basel). 2021 Jul 22;13(15):3679. 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.
在129/Sv-小鼠中，已确定导致过早终止密码子的死端1（Dead-End 1，DND1）突变是原始生殖细胞缺陷的原因，同时伴有先天性睾丸生殖细胞肿瘤（TGCTs）或畸胎瘤的高发病率。作为一种RNA结合蛋白，DND1可以结合mRNA的3'-非翻译区（3'-UTR）并在翻译调控中发挥作用。DND1可以阻止微小RNA（miRNA）接近靶mRNA的3'-UTR，从而抑制miRNA介导的mRNA降解并上调翻译，或者也可以发挥降解或抑制mRNA的作用。DND1活性的其他机制包括促进翻译起始和修饰靶蛋白活性。尽管DND1突变仅在雄性129小鼠中导致自发性TGCT，但当与其他遗传缺陷结合时，它也可以在小鼠中导致卵巢畸胎瘤，或者在WKY/Ztm大鼠品系中导致两性生殖细胞畸胎瘤。此外，对人类细胞系、患者癌组织的研究以及人类癌症基因组分析的应用表明，DND1在多种体细胞癌中可能具有肿瘤抑制或促进功能。在这里，我们综述了DND1在癌症中的作用，包括它在体细胞癌中似乎正在显现的作用。
