Dicer1 is a highly conserved RNaseIII endoribonuclease that plays a critical role in the biogenesis of microRNAs (miRNAs). miRNAs are small regulatory RNAs responsible for post-transcriptional gene silencing, controlling more than half of human protein-coding genes by targeting and regulating complementary RNA transcripts, which is involved in post-transcriptional gene regulation and transposon repression [4].

Pathogenic germline Dicer1 variants cause a hereditary cancer predisposition syndrome. Individuals with such variants may develop a variety of tumors, including pleuropulmonary blastoma, ovarian sex cord-stromal tumors, lung cysts, cystic nephroma, renal sarcoma, Wilms tumor, nodular hyperplasia of the thyroid, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma, genitourinary embryonal rhabdomyosarcoma, and brain tumors like pineoblastoma and pituitary blastoma [1]. In the female genital tract, germline and somatic Dicer1 mutations are associated with rare tumors such as Sertoli-Leydig cell tumor, embryonal rhabdomyosarcoma of the cervix, and others [2]. Dicer1 syndrome encompasses about 20 hamartomatous, hyperplastic or neoplastic conditions, with most not life-threatening, but some being aggressive malignancies [3].

In conclusion, Dicer1 is essential for miRNA biogenesis and post-transcriptional gene regulation. Its germline mutations are associated with a hereditary cancer predisposition syndrome, leading to a wide range of tumors. Understanding Dicer1 through model-based research can help in developing strategies for early detection, surveillance, and treatment of associated diseases [1,2,3,4].