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• W3111152960 abstract "DICER1 is a highly conserved RNaseIII endoribonuclease that has 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. This is achieved through the targeting and regulation of complementary RNA transcripts and has a well-documented role in post-transcriptional gene regulation and transposon repression. DICER1 deficiency results in dysregulation of miRNAs, changing the expression of many genes. DICER1 syndrome represents a collection of benign and malignant tumours arising from an autosomally inherited germline mutation leading to an inherited predisposition to cancer. The syndrome represents an unusual form of Knudson’s two-hit hypothesis, where individuals with a pathogenic germline DICER1 variant acquire a second trans-somatic missense DICER1 mutation. This somatic mutation appears to have to occur in one of five hotspots codons and may contribute towards the incomplete penetrance observed within DICER1 syndrome families. In this case, DICER1 is haploinsuffcient with only one deletion required and partial loss of function being advantageous to tumours over complete loss of function. As increasing data emerge reaffirming the pivotal role of DICER1 in the maintenance of human physiology, DICER1 is likely to become an increasingly attractive target for novel therapeutic strategies." @default.
• W3111152960 created "2020-12-21" @default.
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• W3111152960 date "2020-12-08" @default.
• W3111152960 modified "2023-10-18" @default.
• W3111152960 title "Gene of the month: <i>DICER1:</i> ruler and controller" @default.
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• W3111152960 doi "https://doi.org/10.1136/jclinpath-2020-207203" @default.
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