The cellular requirements of Dicer, an essential miRNA processing enzyme, and the consequences of altered levels of it on tumorigenesis are incompletely understood. We review the effects of Dicer loss in cells of different origin and whether loss of p53 permits cell survival and growth in the absence of Dicer.

Dicer is an RNaseIII-like enzyme that is required for generating short interfering RNAs and microRNAs. The latter have been implicated in regulating cell fate determination in invertebrates and vertebrates. To test the requirement for Dicer in cell-lineage decisions in a mammalian organism, we have generated a conditional allele of dicer-1 (dcr-1) in the mouse. Specific deletion of dcr-1 in the...

Ischemic cardiomyopathy (ICM) is associated with abnormal microRNA expression levels that involve an altered gene profile. However, little known about the underlying causes of disruption in ICM and whether maturation compromised. Therefore, we focused on defects analysis implication biogenesis pathway redox-sensitive microRNAs (redoximiRs). Transcriptomic changes were investigated via ncRNA-seq...

In humans a single species of the RNAseIII enzyme Dicer processes both microRNA precursors into miRNAs and long double-stranded RNAs into small interfering RNAs (siRNAs). An interesting but poorly understood domain of the mammalian Dicer protein is the N-terminal helicase-like domain that possesses a signature DExH motif. Cummins et al. created a human Dicer mutant cell line by inserting an AAV...

Oya Y, Masuzaki R, Tsugawa D, Ray KC, Dou Y, Karp SJ. Dicer-dependent production of microRNA221 in hepatocytes inhibits p27 and is required for liver regeneration in mice. Am J Physiol Gastrointest Liver Physiol 312: G464–G473, 2017. First published February 23, 2017; doi:10.1152/ajpgi.00383.2016.—Dicer processes microRNAs (miRs) into active forms in a wide variety of tissues, including the liv...

Cellular exposure to mild stress (39.5°C-41.5°C) induces thermotolerance, rendering cells resistant to a subsequent heat shock (>42°C) insult. We found that mild hyperthermia at 39.5°C leads to elevations in dicer, a protein well-known for its role in microRNA processing and for its role in cellular stress responses. However, whether elevated dicer protein levels play a role in sustaining a the...

To investigate the role of Dicer and microRNAs in the mammalian CNS, we used mice in which the second RNase III domain of Dicer was conditionally floxed. Conditional Dicer mice were bred with mice expressing an alpha-calmodulin kinase II Cre to selectively inactivate Dicer in excitatory forebrain neurons in vivo. Inactivation of Dicer results in an array of phenotypes including microcephaly, re...

Valproic acid (VPA) is a commonly used drug to treat epilepsy and bipolar disorders. Known properties of VPA are inhibitions of histone deacetylases and activation of extracellular signal regulated kinases (ERK), which cannot fully explain VPA's clinical features. We found that VPA induces the proteasomal degradation of DICER, a key protein in the generation of micro RNAs. Unexpectedly, the con...

Loquacious-PD (Loqs-PD) is required for biogenesis of many endogenous siRNAs in Drosophila In vitro, Loqs-PD enhances the rate of dsRNA cleavage by Dicer-2 and also enables processing of substrates normally refractory to cleavage. Using purified components, and Loqs-PD truncations, we provide a mechanistic basis for Loqs-PD functions. Our studies indicate that the 22 amino acids at the C termin...

Dicer and Drosha are key enzymes in the miRNA-processing pathway which is altered in many human cancers. We analyzed Dicer and Drosha expression levels by quantitative PCR in 151 patients with monoclonal gammopathies: 102 symptomatic myeloma patients, 23 smoldering myelomas and 26 monoclonal gammopathy of undetermined significance. We found that Dicer expression values were significantly higher...