Identification of microRNA-mRNA functional interactions in UVB-induced senescence of human diploid fibroblasts

Greussing, Ruth; Hackl, Matthias; Charoentong, Pornpimol; Pauck, Alexander; Monteforte, Rossella; Cavinato, Maria; Hofer, Edith; Scheideler, Marcel; Neuhaus, Michael; Mičutková, Lucia; Mueck, Christoph; Trajanoski, Zlatko; Grillari, Johannes; Jansen‐Dürr, Pidder

doi:10.1186/1471-2164-14-224

Cited by 59 publications

(49 citation statements)

References 72 publications

(90 reference statements)

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“…Noteworthy, all the studies done previously have been conducted using a single UV irradiation and we are the first one reporting the effect of chronic irradiation on human transcriptome. In our study, we have found that a CLUV treatment induces response to stress as described in previous study [66]. Indeed, our transcriptomic analysis found a deregulation in the ‘‘cell death”; “inflammatory response”; “response to wounding” and “response to stimulus” in the ‘‘response to stress” biological process.…”

Section: Discussionsupporting

confidence: 83%

Influence of a pre-stimulation with chronic low-dose UVB on stress response mechanisms in human skin fibroblasts

et al. 2017

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Exposure to solar ultraviolet type B (UVB), through the induction of cyclobutane pyrimidine dimer (CPD), is the major risk factor for cutaneous cancer. Cells respond to UV-induced CPD by triggering the DNA damage response (DDR) responsible for signaling DNA repair, programmed cell death and cell cycle arrest. Underlying mechanisms implicated in the DDR have been extensively studied using single acute UVB irradiation. However, little is known concerning the consequences of chronic low-dose of UVB (CLUV) on the DDR. Thus, we have investigated the effect of a CLUV pre-stimulation on the different stress response pathways. We found that CLUV pre-stimulation enhances CPD repair capacity and leads to a cell cycle delay but leave residual unrepaired CPD. We further analyzed the consequence of the CLUV regimen on general gene and protein expression. We found that CLUV treatment influences biological processes related to the response to stress at the transcriptomic and proteomic levels. This overview study represents the first demonstration that human cells respond to chronic UV irradiation by modulating their genotoxic stress response mechanisms.

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Section: Discussionsupporting

confidence: 83%

Influence of a pre-stimulation with chronic low-dose UVB on stress response mechanisms in human skin fibroblasts

et al. 2017

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“…Interestingly, the set of miRNAs with reduced expression during DGCR8-mediated arrest are also downregulated during oncogeneinduced senescence (Fig. 4A), replicative senescence (Bonifacio & Jarstfer, 2010;Marasa et al, 2010;Wang et al, 2011;Faraonio et al, 2012) or DNA-damage induced senescence (Greussing et al, 2013) in different strains of human primary fibroblasts. In addition, some of these miRNAs have been shown to bypass oncogene-induced senescence in human fibroblasts or epithelial cells (Voorhoeve et al, 2006;Borgdorff et al, 2010; and are overexpressed in tumors (Ivanovska et al, 2008).…”

Section: Discussionmentioning

confidence: 97%

“…An alternative, noncanonical pathway leads to the generation of pre-miRNA molecules from splicing of intron-encoded precursors, mirtrons, without the participation of the Drosha-DGCR8 complex. pre-miRNAs are subsequently exported to cytoplasm where they are further processed by Dicer and loaded into the RNA-induced silencing complex (RISC) to produce destabilization and translational inhibition of target genes (Guo et al, 2010). Aberrant miRNA expression is a common trend of human cancers.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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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.

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“…The molecular mechanisms underlying UVB induced senescence were investigated in human diploid fibroblasts [34]. Using genome-wide transcriptome analysis, a transcriptional signature of UVB-induced senescence was established.…”

Section: Micrornas and Uv-exposed Skinmentioning

confidence: 99%

MicroRNAs in Skin Response to UV Radiation

Syed

Khan²,

Shabbir³

et al. 2013

CDT

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Solar ultraviolet (UV) radiation, an ubiquitous environmental carcinogen, is classified depending on the wave-length, into three regions; short-wave UVC (200–280 nm), mid-wave UVB (280–320 nm), and long-wave UVA (320–400 nm). The human skin, constantly exposed to UV radiation, particularly the UVB and UVA components, is vulnerable to its various deleterious effects such as erythema, photoaging, immunosuppression and cancer. To counteract these and for the maintenance of genomic integrity, cells have developed several protective mechanisms including DNA repair, cell-cycle arrest and apoptosis. The network of damage sensors, signal transducers, mediators, and various effector proteins is regulated through changes in gene expression. MicroRNAs (miRNAs), a group of small non-coding RNAs, act as post-transcriptional regulators through binding to complementary sequences in the 3′-untranslated region of their target genes, resulting in either translational repression or target degradation. Recent studies show that miRNAs add an additional layer of complexity to the intricately controlled cellular responses to UV radiation. This review summarizes our current knowledge of the role of miRNAs in the regulation of the human skin response upon exposure to UV radiation.

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Identification of microRNA-mRNA functional interactions in UVB-induced senescence of human diploid fibroblasts

Cited by 59 publications

References 72 publications

Influence of a pre-stimulation with chronic low-dose UVB on stress response mechanisms in human skin fibroblasts

Influence of a pre-stimulation with chronic low-dose UVB on stress response mechanisms in human skin fibroblasts

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

MicroRNAs in Skin Response to UV Radiation

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