Regulation of the MicroRNA Processor DGCR8 by the Tumor Suppressor ING1

Gómez-Cabello, Daniel; Callejas, Sergio; Benguría, Alberto; Moreno, Alberto; Alonso, Javier; Palmero, Ignacio

doi:10.1158/0008-5472.can-09-2088

Cited by 35 publications

(37 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar results were obtained with additional human transformed or immortalized cell lines (Fig. S5B, see also Gomez-Cabello et al, 2010). Of note, the upregulation of p21 protein in human tumor or immortalized cells was more intense than that observed in primary fibroblasts (Figs 5A and S5B).…”

Section: Dgcr8 Deficiency Causes Arrest In Cancer Cellssupporting

confidence: 84%

“…Retroviral and lentiviral transductions were performed as previously described (Gomez-Cabello et al, 2010;Abad et al, 2011). pRetroSuper mouse Dgcr8, pSicoR human DGCR8, pSicoR human Dicer, pSicoR human Drosha (Kumar et al, 2007), and relevant empty vectors were obtained from Addgene; pRetroSuper human p53 and pRetroSuper human Rb were a kind gift of Daniel Peeper, NKI, the Netherlands.…”

Section: Retroviral and Lentiviral Infectionmentioning

confidence: 99%

“…cDNA was synthesized using M-MLV reverse transcriptase (Promega, Madison, WI, USA). Quantitative RT-PCR was performed using one microgram of cDNA of each condition, as described (Gomez-Cabello et al, 2010). The primers used are available on request.…”

Section: Quantitative Rt-pcrmentioning

confidence: 99%

See 2 more Smart Citations

DGCR8-mediated disruption of miRNA biogenesis induces cellular senescence in primary fibroblasts

et al. 2013

Self Cite

View full text Add to dashboard Cite

SummaryThe regulation of gene expression by microRNAs (miRNAs) is critical for normal development and physiology. Conversely, miRNA function is frequently impaired in cancer, and other pathologies, either by aberrant expression of individual miRNAs or dysregulation of miRNA synthesis. Here, we have investigated the impact of global disruption of miRNA biogenesis in primary fibroblasts of human or murine origin, through the knockdown of DGCR8, an essential mediator of the synthesis of canonical miRNAs. We find that the inactivation of DGCR8 in these cells results in a dramatic antiproliferative response, with the acquisition of a senescent phenotype. Senescence triggered by DGCR8 loss is accompanied by the upregulation of the cell-cycle inhibitor p21CIP1. We further show that a subset of senescence-associated miRNAs with the potential to target p21CIP1 is downregulated during DGCR8-mediated senescence. Interestingly, the antiproliferative response to miRNA biogenesis disruption is retained in human tumor cells, irrespective of p53 status. In summary, our results show that defective synthesis of canonical microRNAs results in cell-cycle arrest and cellular senescence in primary fibroblasts mediated by specific miRNAs, and thus identify global miRNA disruption as a novel senescence trigger.

show abstract

Section: Dgcr8 Deficiency Causes Arrest In Cancer Cellssupporting

confidence: 84%

Section: Retroviral and Lentiviral Infectionmentioning

confidence: 99%

See 1 more Smart Citation

DGCR8-mediated disruption of miRNA biogenesis induces cellular senescence in primary fibroblasts

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Alterations of DROSHA and DGCR8 expressions affect the levels of some miRNAs via modulating the activity of the microprocessor complex [36][37][38]. In view of our recent findings that partial pre-miRNAs expression alters in Fmr1-deficient mice [30], we propose that FMRP might be involved in pri-miRNAs processing by regulating DROSHA or DGCR8 expressions.…”

Section: Fmrp Post-transcriptionally Upregulates Drosha Expressionmentioning

confidence: 80%

Involvement of FMRP in Primary MicroRNA Processing via Enhancing Drosha Translation

et al. 2016

View full text Add to dashboard Cite

Fragile X mental retardation protein (FMRP), associated with fragile X syndrome, is known as an RNA-binding protein to regulate gene expression at post-transcriptional level in the brain. FMRP is also involved in microRNA (miRNA) biogenesis during the process of precursor miRNA (pre-miRNA) into mature miRNA. However, there is no description of the effect of FMRP on primary miRNA (pri-miRNA) processing. Here, we uncover a novel role of FMRP in pri-miRNA processing via controlling Drosha translation. We show that the expression of DROSHA protein, instead of its messenger RNA (mRNA) transcripts, is downregulated in both the hippocampus of Fmr1-knockout mice and the FMRP-knockdown Neuro-2a cells. Overexpression or knockdown FMRP does not alter Drosha mRNA stability. Immunoprecipitation and polysome analyses demonstrate that FMRP binds to the Drosha mRNA and enhances its translation. Additionally, we show that loss of FMRP in Fmr1-deficient mice results in the accumulation of three in six analyzed pri-miRNAs and the reduction of the corresponding pre-miRNAs and mature miRNAs. Thus, our data suggest that FMRP is involved in pri-miRNA processing via enhancing DROSHA expression that may play an important role in fragile X syndrome.

show abstract

“…Specifi cally, ectopic expression of ING1 resulted in decreased promoter activity of the DGCR8 gene, which encodes a microRNA processor that cleaves pre-miRNAs involved in cell proliferation for export to the cytoplasm (Gomez-Cabello et al 2010 ). Expression of INGs can also be inhibited by microRNAs.…”

Section: Ings and Short Non-coding Rnasmentioning

confidence: 99%

Function of the ING Proteins in Cancer and Senescence

Tran

Rajarajacholan

Riabowol

2013

Tumor Dormancy, Quiescence, and Senescence, Volume 2

View full text Add to dashboard Cite

Age is one of the strongest correlates to the incidence of cancers known, suggesting that the two processes are linked. Cell aging (senescence) is increasingly being linked to epigenetic pathways, many of which have recently been found to be markedly altered in precancerous and cancer cells. Thus, misregulation of epigenetic pathways may impact both cancer and aging by infl uencing genetic and biochemical pathways common to both processes. Similar to the p53 and retinoblastoma (Rb) tumor suppressors that affect chromatin structure by genetic and epigenetic mechanisms, the IN hibitor of G rowth (ING) type II tumour suppressors affect pathways that contribute to cell aging and cancer. In particular, the INGs have been demonstrated to act as readers of the histone code by virtue of interacting specifi cally with the histone H3 residue H3K4Me3 and as targeting subunits of the writers of the histone code by being stoichiometric members of histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes. The ING proteins are frequently

show abstract

Regulation of the MicroRNA Processor DGCR8 by the Tumor Suppressor ING1

Cited by 35 publications

References 41 publications

DGCR8-mediated disruption of miRNA biogenesis induces cellular senescence in primary fibroblasts

DGCR8-mediated disruption of miRNA biogenesis induces cellular senescence in primary fibroblasts

Involvement of FMRP in Primary MicroRNA Processing via Enhancing Drosha Translation

Function of the ING Proteins in Cancer and Senescence

Contact Info

Product

Resources

About