A5065735989- Cancer-related molecular mechanisms research
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- RNA modifications and cancer
- MicroRNA in disease regulation
- Extracellular vesicles in disease
- Neuroblastoma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Cancer, Hypoxia, and Metabolism
- Organoselenium and organotellurium chemistry
- Hippo pathway signaling and YAP/TAZ
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Selenium in Biological Systems
- Hepatitis C virus research
- RNA Interference and Gene Delivery
- Cancer-related Molecular Pathways
- Liver Disease Diagnosis and Treatment
- Circular RNAs in diseases
- Dialysis and Renal Disease Management
- Synthesis and Characterization of Heterocyclic Compounds
- Genetic Syndromes and Imprinting
- Cellular Mechanics and Interactions
- Cancer Research and Treatments
Istituto Pasteur
2016-2025
Sapienza University of Rome
2016-2025
Despite clear evidence that exosomal microRNAs (miRNAs) are able to modulate the cellular microenvironment and RNA cargo selection is deregulated in pathological conditions, mechanisms controlling specific sorting into extracellular vesicles still poorly understood. Here, we identified binding protein SYNCRIP (synaptotagmin-binding cytoplasmic RNA-interacting protein; also known as hnRNP-Q or NSAP1) a component of hepatocyte miRNA machinery. knockdown impairs miRNAs exosomes. Furthermore,...
The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing broad repertoire epithelial genes. How chromatin modifiers instrumental to its activity are recruited Snail-specific binding sites unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates physical interaction between enhancer zeste homolog 2 (EZH2), an enzymatic subunit...
Exosomal miRNA transfer is a mechanism for cell-cell communication that important in the immune response, functioning of nervous system and cancer. Syncrip/hnRNPQ highly conserved RNA-binding protein mediates exosomal partition set miRNAs. Here, we report Syncrip's amino-terminal domain, which was previously thought to mediate protein-protein interactions, cryptic, sequence-specific designated NURR (N-terminal unit RNA recognition). The domain specific recognition short hEXO sequence...
Alzheimer's disease (AD) has a complex and not-fully-understood etiology. Recently, the serotonin receptor 5-HT6 emerged as promising target for AD treatment; thus, here new series of 5-HT6R ligands with 1,3,5-triazine core selenoether linkers was explored. Among them, 2-naphthyl derivatives exhibited strong affinity selectivity over 5-HT1AR (13–15), 5-HT7R (14 15), 5-HT2AR (13). Compound 15 displayed high other central nervous system receptors low risk cardio-, hepato-, nephrotoxicity no...
In many cell types, several cellular processes, such as differentiation of stem/precursor cells, maintenance differentiated phenotype, motility, adhesion, growth, and survival, strictly depend on the stiffness extracellular matrix that, in vivo , characterizes their correspondent organ tissue. liver, stromal rigidity is essential to obtain correct physiology whereas any alteration causes liver dysfunctions. The substrate an element no longer negligible for cultivation so that data far...
The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis progression hepatocellular carcinoma gastrointestinal cancers. Furthermore, functional studies revealed a pivotal role for epithelial-to-mesenchymal transition, as this causal repressive activity master factor SNAIL on genes. Despite proven oncogenic HOTAIR, its transcriptional regulation still poorly understood....
Since the histone modifying enzymes EZH2 and HDACs control a number of epigenetic-dependent carcinogenic pathways, we designed first-in-class dual EZH2/HDAC inhibitor 5 displaying (sub)micromolar inhibition against both targets. When tested in several cancer cell lines, hybrid impaired viability at low micromolar level leukemia U937 rhabdomyosarcoma RH4 cells provided G1 arrest, apoptotic induction, increased differentiation, associated with an increase acetyl-H3 acetyl-α-tubulin decrease...
Despite their emerging relevance to fully understand disease pathogenesis, we have as yet a poor understanding how biomechanical signals are integrated with specific biochemical pathways determine cell behaviour. Mesothelial-to-mesenchymal transition (MMT) markers colocalized TGF-β1-dependent signaling and yes-associated protein (YAP) activation across biopsies from different pathologies exhibiting peritoneal fibrosis, supporting mechanotransduction central driving component of these class...
Epitranscriptomics represents a further layer of gene expression regulation. Specifically, N6-methyladenosine (m6A) regulates RNA maturation, stability, degradation, and translation. Regarding microRNAs (miRNAs), while it has been reported that m6A impacts their biogenesis, the functional effects on mature miRNAs remain unclear. Here, we show modification specific weakens coupling to AGO2, impairs function target mRNAs, determines delivery into extracellular vesicles (EVs), provides...
Epithelial-to-mesenchymal transition (EMT) and the reverse mesenchymal-to-epithelial (MET) are manifestations of cellular plasticity that imply a dynamic profound gene expression reprogramming. While major epigenetic code controlling coordinated regulation whole transcriptional profile is guaranteed by DNA methylation, methyltransferase (DNMT) activities in EMT/MET dynamics still largely unexplored. Here, we investigated molecular mechanisms directly linking HNF4α, master effector MET, to...
Abstract HOTAIR is a lncRNA overexpressed in several epithelial cancers and strongly correlated with invasion. This was proven pivotal element of the epithelial-to-mesenchymal transition (EMT), transdifferentiation process triggering metastasis. Snail, master inducer EMT, requires to recruit EZH2 on specific target genes (i.e., HNF4α, E-cadherin, HNF1α) cause their repression. Here, we designed deletion mutant form, named HOTAIR-sbid, including putative Snail-binding domain but depleted...
Abstract Background DNA methyltransferases (DNMTs) are epigenetic enzymes involved in embryonic development, cell differentiation, epithelial to mesenchymal transition, and control of gene expression, whose overexpression or enhanced catalytic activity has been widely reported cancer initiation progression. To date, two DNMT inhibitors (DNMTi), 5-azacytidine (5-AZA) 5-aza-2′-deoxycytidine (DAC), approved for the treatment myelodysplastic syndromes acute myeloid leukemia. Nevertheless, they...
•HCV T0/T6 EVs have been functionally and structurally compared to HD EVs.•HD ameliorate LX2 cells' fibrogenic phenotype while HCV do not.•HCV contain lower levels of antifibrogenic miRNAs EVs.•HCV EVs' cargo is enriched in profibrogenic proteins (e.g. DIAPH1).•SVR does not restore activity EVs. Background & AimsPatients with who achieve a sustained virological response (SVR) on direct-acting antiviral (DAA) therapy still need be monitored for signs liver disease progression. To this end,...
Abstract Background & Aims Hepatitis C virus ( HCV ) infection is known to cause major alterations in the cross‐talk between hepatic and immune cells thus contributing liver disease pathogenesis. Extracellular vesicles have been proved act as players cell‐cell communication, their cargo changes relation pathophysiological states. The aim of this study was evaluate effects chronic direct‐acting antivirals DAA on exosome‐delivered micro RNA s ability modulate innate response. Methods...
The still largely obscure molecular events in the glioblastoma oncogenesis, a primary brain tumor characterized by an inevitably dismal prognosis, impel for investigation. importance of Long noncoding RNAs as regulators gene expression has recently become evident. Among them, H19 recognized oncogenic role several types human tumors and was shown to correlate some aspects cells. Here we, hypothesyze that exerts its function through interaction with catalytic subunit PRC2 complex, EZH2. By...
Yes-associated protein (YAP) is a transcriptional co-factor involved in many cell processes, including development, proliferation, stemness, differentiation, and tumorigenesis. It has been described as sensor of mechanical biochemical stimuli that enables cells to integrate environmental signals. Although the liver correlation between extracellular matrix elasticity (greatly increased most chronic hepatic diseases), differentiation/functional state parenchymal subcellular...
In this study, we explored whether Nutlin-3a, a well-known, nontoxic small-molecule compound antagonizing the inhibitory interaction of MDM2 with tumor suppressor p53, may restore ligands for natural killer (NK) cell-activating receptors (NK-AR) on neuroblastoma cells to enhance NK cell-mediated killing. Neuroblastoma cell lines were treated and expression NKG2D DNAM-1 NK-ARs susceptibility evaluated. Adoptive transfer human in xenograft neuroblastoma-bearing NSG murine model was assessed....
The mitochondrial SIRT3 modulates several biological pathways such as cancer, metabolism, and hypoxia-related diseases. Recently, we discovered new 1,4-dihydropyridines, compounds 2 3, the latter being a SIRT3-specific activator. In present work, novel 2- 3-related small series of have been developed, with 3c displaying strongest binding activation, KD 29 μM 387% enzyme activation. Differently, 3d was best in enhancing glutamate dehydrogenase activity deacetylating K68- K122-acMnSOD...