Comparative Analysis of Gene Expression Data Reveals Novel Targets of Senescence-Associated microRNAs

In the last decades, cellular senescence is viewed as a complex mechanism involved in different processes, ranging from tumor suppression to induction of age-related degenerative alterations. Senescence-inducing stimuli are myriad and, recently, we and others have demonstrated the role exerted by microRNAs in the induction and maintenance of senescence, by the identification of a subset of Senescence-Associated microRNAs (SAmiRs) up-regulated during replicative or stress-induced senescence and able to induce a premature senescent phenotype when over-expressed in human primary cells. With the intent to find novel direct targets of two specific SAmiRs, SAmiR-494 and -486-5p, and cellular pathways which they are involved in, we performed a comparative analysis of gene expression profiles available in literature to select genes down-regulated upon replicative senescence of human primary fibroblasts. Among them, we searched for SAmiR’s candidate targets by analyzing with different target prediction algorithms their 3’UTR for the presence of SAmiR-binding sites. The expression profiles of selected candidates have been validated on replicative and stress-induced senescence and the targeting of the 3’UTRs was assessed by luciferase assay. Results allowed us to identify Cell Division Cycle Associated 2 (CDCA2) and Inhibitor of DNA binding/differentiation type 4 (ID4) as novel targets of SAmiR-494 and SAmiR-486-5p, respectively. Furthermore, we demonstrated that the over-expression of CDCA2 in human primary fibroblasts was able to partially counteract etoposide-induced senescence by mitigating the activation of DNA Damage Response

Il suolo ci regala tanto. Non calpestiamolo

LIFE + SAM4CP “Soil Administration Model 4 Community Profit” (www.sam4cp.com), aims to demonstrate that the planning and regulation of land use require the integration of policies for the protection of soil resources and evaluation the economic implications, in terms of cost/benefit, their impact on the ecosystemic functions of the resource itself. With effects on the production capacity, availability of raw materials, biodiversity, carbon cycle, water cycle, landscape heritage and environmental functions of rural areas and the hydrogeological hazards. The project aims to propose simulation models on the impacts of soil sealing both the consequences, regarding ecosystem and economic, for the community, to be used in the context of urban planning and policies of government land

A Common Mechanism Underlying the E1A Repression and the cAMP Stimulation of the H Ferritin Transcription

Transcription of the H ferritin gene in vivo is stimulated by cAMP and repressed by the E1A oncoprotein. We report here the identification of the cis-element in the human promoter responsive to both cAMP- and E1A-mediated signals. This promoter region is included between positions -62 to -45 and binds a approximate 120-kDa transcription factor called Bbf. Bbf forms a complex in vivo with the coactivator molecules p300 and CBP. Recombinant E1A protein reduces the formation of these complexes. In vivo overexpression of p300 in HeLa cells reverses the E1A-mediated inhibition of the ferritin promoter transcription driven by Bbf. These data suggest the existence of a common mechanism for the cAMP activation and the E1A-mediated repression of H ferritin transcription