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Università della Svizzera italiana

Exon–Intron differential analysis reveals the role of competing endogenous RNAs in post-transcriptional regulation of translation

Munz, Nicolas ; Cascione, Luciano ; Parmigiani, Luca ; Tarantelli, Chiara ; Rinaldi, Andrea ; Cmiljanovic, Natasa ; Cmiljanovic, Vladimir ; Giugno, Rosalba ; Bertoni, Francesco ; Napoli, Sara

In: Non-coding RNA, 2021, vol. 7, no. 2, p. 13

Stressful conditions induce the cell to save energy and activate a rescue program modulated by mammalian target of rapamycin (mTOR). Along with transcriptional and translational regulation, the cell relies also on post-transcriptional modulation to quickly adapt the translation of essential proteins. MicroRNAs play an important role in the regulation of protein translation, and their...

Università della Svizzera italiana

Biological and clinical implications of BIRC3 mutations in chronic lymphocytic leukemia

Diop, Fary ; Moia, Riccardo ; Favini, Chiara ; Spaccarotella, Elisa ; De Paoli, Lorenzo ; Bruscaggin, Alessio ; Spina, Valeria ; Terzi-di-Bergamo, Lodovico ; Arruga, Francesca ; Tarantelli, Chiara ; Deambrogi, Clara ; Rasi, Silvia ; Adhinaveni, Ramesh ; Patriarca, Andrea ; Favini, Simone ; Sagiraju, Sruthi ; Jabangwe, Clive ; Kodipad, Ahad A. ; Peroni, Denise ; Mauro, Francesca R. ; Del Giudice, Ilaria ; Forconi, Francesco ; Cortelezzi, Agostino ; Zaja, Francesco ; Bomben, Riccardo ; Rossi, Francesca Maria ; Visco, Carlo ; Chiarenza, Annalisa ; Rigolin, Gian Matteo ; Marasca, Roberto ; Coscia, Marta ; Perbellini, Omar ; Tedeschi, Alessandra ; Laurenti, Luca ; Motta, Marina ; Donaldson, David ; Weir, Phil ; Mills, Ken ; Thornton, Patrick ; Lawless, Sarah ; Bertoni, Francesco ; Del Poeta, Giovanni ; Cuneo, Antonio ; Follenzi, Antonia ; Gattei, Valter ; Boldorini, Renzo Luciano ; Catherwood, Mark ; Deaglio, Silvia ; Foà, Robin ; Gaidano, Gianluca ; Rossi, Davide

In: Haematologica, 2020, vol. 105, no. 2, p. 448-456

BIRC3 is a recurrently mutated gene in chronic lymphocytic leukemia (CLL) but the functional implications of BIRC3 mutations are largely unexplored. Furthermore, little is known about the prognostic impact of BIRC3 mutations in CLL cohorts homogeneously treated with first-line fludarabine, cyclophosphamide, and rituximab (FCR). By immunoblotting analysis, we showed that the non-canonical...

Università della Svizzera italiana

Role of ETS1 in the transcriptional network of diffuse large B cell lymphoma of the activated B cell-like type

Priebe, Valdemar ; Sartori, Giulio ; Napoli, Sara ; Chung, Elaine Yee Lin ; Cascione, Luciano ; Kwee, Ivo ; Arribas, Alberto Jesus ; Mensah, Afua Adjeiwaa ; Rinaldi, Andrea ; Ponzoni, Maurilio ; Zucca, Emanuele ; Rossi, Davide ; Efremov, Dimitar ; Lenz, Georg ; Thome, Margot ; Bertoni, Francesco

In: Cancers, 2020, vol. 12, no. 7, p. 17 p

Diffuse large B cell lymphoma (DLBCL) is a heterogenous disease that has been distinguished into at least two major molecular entities, the germinal center-like B cell (GCB) DLBCL and activated-like B cell (ABC) DLBCL, based on transcriptome expression profiling. A recurrent ch11q24.3 gain is observed in roughly a fourth of DLBCL cases resulting in the overexpression of two ETS transcription...

Università della Svizzera italiana

The novel TORC1/2 kinase inhibitor PQR620 has anti-tumor activity in lymphomas as a single agent and in combination with venetoclax

Tarantelli, Chiara ; Gaudio, Eugenio ; Hillmann, Petra ; Spriano, Filippo ; Sartori, Giulio ; Aresu, Luca ; Cascione, Luciano ; Rageot, Denise ; Kwee, Ivo ; Beaufils, Florent ; Zucca, Emanuele ; Stathis, Anastasios ; Wymann, Matthias P. ; Cmiljanovic, Vladimir ; Fabbro, Doriano ; Bertoni, Francesco

In: Cancers, 2019, vol. 11, no. 6, p. 775

The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling cascade is an important therapeutic target for lymphomas. Rapamycin-derivates as allosteric mTOR complex 1 (TORC1) inhibitors have shown moderate preclinical and clinical anti-lymphoma activity. Here, we assessed the anti-tumor activity of PQR620, a novel brain penetrant dual TORC1/2 inhibitor, in 56...

Università della Svizzera italiana

Long non-coding RNAs as molecular signatures for canine B-Cell lymphoma characterization

Cascione, Luciano ; Giudice, Luca ; Ferraresso, Serena ; Marconato, Laura ; Giannuzzi, Diana ; Napoli, Sara ; Bertoni, Francesco ; Giugno, Rosalba ; Aresu, Luca

In: Non-coding RNA, 2019, vol. 5, no. 3, p. 47

Diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) and follicular lymphoma (FL) are the most common B-cell lymphomas (BCL) in dogs. Recent investigations have demonstrated overlaps of these histotypes with the human counterparts, including clinical presentation, biologic behavior, tumor genetics, and treatment response. The molecular mechanisms that underlie canine BCL are...

Università della Svizzera italiana

Is there a role for dual PI3K/mTOR inhibitors for patients affected with lymphoma?

Tarantelli, Chiara ; Lupia, Antonio ; Stathis, Anastasios ; Bertoni, Francesco

In: International journal of molecular sciences, 2020, vol. 21, no. 3, p. 21 p

The activation of the PI3K/AKT/mTOR pathway is a main driver of cell growth, proliferation, survival, and chemoresistance of cancer cells, and, for this reason, represents an attractive target for developing targeted anti- cancer drugs. There are plenty of preclinical data sustaining the anti-tumor activity of dual PI3K/mTOR inhibitors as single agents and in combination in lymphomas. Clinical...

Università della Svizzera italiana

Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence

Revandkar, Ajinkya ; Perciato, Maria Luna ; Toso, Alberto ; Alajati, Abdullah ; Chen, Jingjing ; Gerber, Hermeto ; Dimitrov, Mitko ; Rinaldi, Andrea ; Delaleu, Nicolas ; Pasquini, Emiliano ; D’Antuono, Rocco ; Pinton, Sandra ; Losa, Marco ; Gnetti, Letizia ; Arribas, Alberto ; Fraering, Patrick ; Bertoni, Francesco ; Nepveu, Alain ; Andrea Alimonti

In: Nature communications, 2016, vol. 7, p. 13719

Activation of NOTCH signalling is associated with advanced prostate cancer and treatment resistance in prostate cancer patients. However, the mechanism that drives NOTCH activation in prostate cancer remains still elusive. Moreover, preclinical evidence of the therapeutic efficacy of NOTCH inhibitors in prostate cancer is lacking. Here, we provide evidence that PTEN loss in prostate tumours ...

Università della Svizzera italiana

Dnmt3a restrains mast cell inflammatory responses

Leoni, Cristina ; Montagner, Sara ; Rinaldi, Andrea ; Bertoni, Francesco ; Polletti, Sara ; Balestrieri, Chiara ; Monticelli, Silvia

In: Proceedings of the national academy of sciences, 2017, vol. 114, no. 8, p. E1490-E1499

DNA methylation and specifically the DNA methyltransferase enzyme DNMT3A are involved in the pathogenesis of a variety of hematological diseases and in regulating the function of immune cells. Although altered DNA methylation patterns and mutations in DNMT3A correlate with mast cell proliferative disorders in humans, the role of DNA methylation in mast cell biology is not understood. By using...

Università della Svizzera italiana

ACKR3 expression on diffuse large B cell lymphoma is required for tumor spreading and tissue infiltration

Puddinu, Viola ; Casella, Sabrina ; Radice, Egle ; Thelen, Sylvia ; Dirnhofer, Stefan ; Bertoni, Francesco ; Thelen, Marcus

In: Oncotarget, 2017, vol. 8, no. 49, p. 85068-85084

Diffuse large B cell lymphoma (DLBCL) is the most frequent lymphoma accounting for more than the 30% of the cases. Involvement of extranodal sites, such as bone marrow and central nervous system, is associated with poor prognosis. A contribution of the chemokine system in these processes is assumed as it is known as a critical regulator of the metastatic process in cancer. The atypical...

Università della Svizzera italiana

Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides

Bergmann, Timothy J. ; Fregno, Ilaria ; Fumagalli, Fiorenza ; Rinaldi, Andrea ; Bertoni, Francesco ; Boersema, Paul J. ; Picotti, Paola ; Molinari, Maurizio

In: Journal of biological chemistry, 2018, vol. 293, no. 15, p. 5600-5612

The stress sensors ATF6, IRE1, and PERK monitor deviations from homeostatic conditions in the endoplasmic reticulum (ER), a protein biogenesis compartment of eukaryotic cells. Their activation elicits unfolded protein responses (UPR) to reestablish proteostasis. UPR have been extensively investigated in cells exposed to chemicals that activate ER stress sensors by perturbing calcium, N-glycans,...