Non-coding Genome - Francesco Nicassio
MicroRNAs and non-coding RNAs in Development and DiseaseThe Non-coding Genome Group studies the function and regulation of non-coding transcripts, focusing on the molecular mechanisms in control of gene expression regulation and how they shape the identity and properties of human stem cells during cancer evolution
WHAT? understanding the role played by ncRNAs in transcriptional/epigenetic plasticity
WHERE? physiology (development) and human (cancer) disease, focusing on cancer evolution (drug resistance, metastasis)
HOW? integration of Experimental models with Computational and –omics methodologies
High-resolution characterization of the transcriptional/epigenetic landscape of breast cancer organoids
Cancer organoids recapitulate cancer cell growth in vitro within a 3D environment. Able to copycat the 3D spatial tissue organization and catch the genetic and phenotypic heterogeneity of their tissue of origin, organoids represent a more reliable platform than 2D cultures for studying cancer progression and drug resistance mechanisms. We aim at investigating the role non-coding RNAs and DNA elements play in the adaptive response of breast cancer cells following anticancer therapies and in the context of tumor organoids We will use cutting-edge genomic approaches to achieve a high-resolution characterization of the transcriptional/epigenetic landscape of breast cancer organoids. We will focus on the evolutionary trajectories of the different tumour subpopulations that will be characterized both in basal conditions (homeostasis) and in response to anticancer treatments, stimulating adaptive response mechanisms. The goal will be to gain insight into the genetic and epigenetic factors that hinder the success of established anticancer therapies.
Identification of the host proteins interacting with SARS-CoV-2 RNA
SARS-CoV-2 is a positive single-stranded RNA virus which interacts at different stages with the host proteins of infected cells. These interactions are necessary for the host to recognize and block the replication of the virus. But, at the same time, the virus requires host proteins to translate, transcribe and replicate its genetic material. In order to identify the host proteins that interact with SARS-CoV-2 RNA, we adopted the RNA-protein interaction detection coupled to mass spectrometry (RaPID-MS) technology, which allows the purification and identification by MS-based proteomics of the proteins associated to a specific RNA of interest expressed in mammalian cells. In particular, we conducted the analysis on the more structured regions of SARS-CoV-2 RNA and retrieved several proteins specifically associated with each region. Overall, our data revealed a list of proteins associated to SARS-CoV-2 RNA that will be further characterized to understand their role in SARS-CoV-2 infection and viral replication.
CRISPRi screening of LncRNAs in Transcriptional Reprogramming of Breast Cancer Cells
Long non-coding RNAs (lncRNAs) are emerging as promising novel diagnostic and therapeutic molecules. These transcripts provide a flexible and dynamic mechanism of gene expression regulation. Emerging evidence suggests a role for lncRNAs as key components in adaptation pathways. In breast cancer, transcriptional adaptation has been described to occur, in particular during the acquisition of chemoresistance. Unfortunately, the mechanisms behind cancer adaptation and the role lncRNAs play are still to be clarified. We are currently characterizing the role of a group of lncRNAs during adaptive responses in triple-negative breast cancer cells by means of CRISPRinterference. We are functionalizing lncRNAs in a classic-drop out screening during proliferation, drug response and in vivo tumorigenesis. In parallel, we are characterizing the transcriptomic response of lncRNAs modulation by single cell-RNAseq in a CROP-seq like setting. With this work, we will bring novel knowledge into the regulatory framework played by lncRNAs in cancer cell plasticity.
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Simeone I, Rubolino C, Noviello T, Farinello D, Cerulo L, Marzi MJ, Nicassio F. Prediction and pan-cancer analysis of mammalian transcripts involved in target directed miRNA degradation Nucleic Acids Res. 2022
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Bido S, Muggeo S, Massimino L, Marzi MJ, Giannelli SG, Melacini E, Nannoni M, Gambarè D, Bellini E, Ordazzo G, Rossi G, Maffezzini C, Iannelli A, Luoni M, Bacigaluppi M, Gregori S, Nicassio F, Broccoli V. Microglia-specific overexpression of α-synuclein leads to severe dopaminergic neurodegeneration by phagocytic exhaustion and oxidative toxicity. Nat Commun. 2021
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Tordonato C, Marzi MJ, Giangreco G, Freddi S, Bonetti P, Tosoni D, Di Fiore PP, Nicassio F miR-146 connects stem cell identity with metabolism and pharmacological resistance in breast cancer J Cell Biol. 2021
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Spadotto V, Giambruno R, Massignani E, Mihailovich M, Maniaci M, Patuzzo F, Ghini F, Nicassio F, Bonaldi T. PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis Nucleic Acids Res. 2020
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Pons-Espinal M, Gasperini C, Marzi MJ, Braccia C, Armirotti A, Pötzsch A, Walker TL, Fabel K, Nicassio F, Kempermann G, De Pietri Tonelli D. MiR-135a-5p Is Critical for Exercise-Induced Adult Neurogenesis Stem Cell Reports. 2019
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Rossi M, Bucci G, Rizzotto D, Bordo D, Marzi MJ, Puppo M, Flinois A, Spadaro D, Citi S, Emionite L, Cilli M, Nicassio F, Inga A, Briata P, Gherzi R. LncRNA EPR controls epithelial proliferation by coordinating Cdkn1a transcription and mRNA decay response to TGF-β Nat Commun. 2019
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Panebianco F, Climent M, Malvindi MA, Pompa PP, Bonetti P, Nicassio F Delivery of biologically active miR-34a in normal and cancer mammary epithelial cells by synthetic nanoparticles Nanomedicine 2019
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Santoro A, Vlachou T, Luzi L, Melloni G, Mazzarella L, D'Elia E, Aobuli X, Pasi CE, Reavie L, Bonetti P, Punzi S, Casoli L, Sabò A, Moroni MC, Dellino GI, Amati B, Nicassio F, Lanfrancone L, Pelicci PG. p53 Loss in Breast Cancer Leads to Myc Activation, Increased Cell Plasticity, and Expression of a Mitotic Signature with Prognostic Value Cell Rep. 2019
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Bonetti P, Climent M, Panebianco F, Tordonato C, Santoro A, Marzi MJ, Pelicci PG, Ventura A, Nicassio F. Dual role for miR-34a in the control of early progenitor proliferation and commitment in the mammary gland and in breast cancer Oncogene 2019
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Ghini F, Rubolino C, Climent M, Simeone I, Marzi MJ, Nicassio F. Endogenous Transcripts control miRNA levels and activity in mammalian cells by target-directed miRNA degradation Nature Communications 2018
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Culurgioni S, Mari S, Bonetti P, Gallini S, Bonetto G, Brennich M, Round A, Nicassio F, Mapelli M. Insc:LGN tetramers promote asymmetric divisions of mammary stem cells Nature Communications 2018
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Pons-Espinal M, de Luca E, Marzi MJ, Beckervordersandforth R, Armirotti A, Nicassio F, Fabel K, Kempermann G, De Pietri Tonelli D. Synergic Functions of miRNAs Determine Neuronal Fate of Adult Neural Stem Cells Stem Cell Reports 2017
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Marinaro F, Marzi MJ, Hoffmann N, Amin H, Pelizzoli R, Niola F, Nicassio F, De Pietri Tonelli D. MicroRNA-independent functions of DGCR8 are essential for neocortical development and TBR1 expression EMBO Reports 2017
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Marzi MJ, Montani F, Carletti RM, Dezi F, Dama E, Bonizzi G, Sandri MT, Rampinelli C, Bellomi M, Maisonneuve P, Spaggiari L, Veronesi G, Bianchi F, Di Fiore PP, Nicassio F. Optimization and Standardization of Circulating MicroRNA Detection for Clinical Application: The miR-Test Case Clinical Chemistry 2016
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Marzi MJ, Ghini F, Cerruti B, de Pretis S, Bonetti P, Giacomelli C, Gorski MM, Kress T, Pelizzola M, Muller H, Amati B, Nicassio F. Degradation dynamics of microRNAs revealed by a novel pulsechase approach Genome Research 2016