Department of Human Genetics, Medicine, McGill University, Montreal, QC, Canada; Cancer Axis, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada; Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
Molecular Mechanisms and Experimental Therapy in Oncology Program - Oncobell, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada.
Trends Genet. 2023 May;39(5):401-414. doi: 10.1016/j.tig.2023.01.009. Epub 2023 Feb 28.
MicroRNAs (miRNAs) play vital roles in the regulation of gene expression, a process known as miRNA-induced gene silencing. The human genome codes for many miRNAs, and their biogenesis relies on a handful of genes, including DROSHA, DGCR8, DICER1, and AGO1/2. Germline pathogenic variants (GPVs) in these genes cause at least three distinct genetic syndromes, with clinical manifestations that range from hyperplastic/neoplastic entities to neurodevelopmental disorders (NDDs). Over the past decade, DICER1 GPVs have been shown to lead to tumor predisposition. Moreover, recent findings have provided insight into the clinical consequences arising from GPVs in DGCR8, AGO1, and AGO2. Here we provide a timely update with respect to how GPVs in miRNA biogenesis genes alter miRNA biology and ultimately lead to their clinical manifestations.
微小 RNA（miRNA）在基因表达调控中发挥着重要作用，这一过程被称为 miRNA 诱导的基因沉默。人类基因组编码了许多 miRNA，其生物发生依赖于少数基因，包括 DROSHA、DGCR8、DICER1 和 AGO1/2。这些基因中的种系致病性变异（GPV）至少导致三种不同的遗传综合征，临床表现从增生/肿瘤实体到神经发育障碍（NDD）不等。在过去的十年中，已经表明 DICER1 GPV 导致肿瘤易感性。此外，最近的发现提供了对 DGCR8、AGO1 和 AGO2 中 GPV 引起的临床后果的深入了解。在这里，我们提供了一个关于 miRNA 生物发生基因中的 GPV 如何改变 miRNA 生物学并最终导致其临床表现的及时更新。
