Long non-coding RNA mitophagy and ALK-negative anaplastic lymphoma-associated transcript: a novel regulator of mitophagy in T-cell lymphoma
Valentina Mularoni,
Benedetta Donati,
Annalisa Tameni,
Veronica Manicardi,
Francesca Reggiani,
Elisabetta Sauta,
Magda Zanelli,
Marco Tigano,
Emanuele Vitale,
Federica Torricelli,
Stefano Ascani,
Giovanni Martino,
Giorgio Inghirami,
Francesca Sanguedolce,
Alessia Ruffini,
Alberto Bavieri,
Stefano Luminari,
Marco Pizzi,
Angelo Paolo Dei Tos,
Cinzia Fesce,
Antonino Neri,
Alessia Ciarrocchi,
Valentina Fragliasso
Affiliations
Valentina Mularoni
Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia
Benedetta Donati
Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia
Annalisa Tameni
Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia
Veronica Manicardi
Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia
Francesca Reggiani
Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, Viale Risorgimento 80, 42123, Reggio Emilia
Elisabetta Sauta
IRCCS Humanitas Clinical and Research Center, Milan
Magda Zanelli
Pathology Unit, Department of Oncology, Oncology, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia
Marco Tigano
Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA
Emanuele Vitale
Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy; Clinical and Experimental Medicine Ph.D. Program, University of Modena and Reggio Emilia, Modena
Federica Torricelli
Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia
Stefano Ascani
Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, Terni
Giovanni Martino
Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, Terni, Italy; Institute of Hematology and CREO, University of Perugia, Perugia
Giorgio Inghirami
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
Francesca Sanguedolce
Pathology Unit, Policlinico Riuniti, University of Foggia, Foggia
Alessia Ruffini
Hematology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia
Alberto Bavieri
Hematology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia
Stefano Luminari
Hematology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia
Marco Pizzi
Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, Padova
Angelo Paolo Dei Tos
Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, Padova
Cinzia Fesce
Hematology Unit, University Hospital, Foggia
Antonino Neri
Scientific Directorate, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia
Alessia Ciarrocchi
Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia
Valentina Fragliasso
Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia
Long non-coding RNA (lncRNA) are emerging as powerful and versatile regulators of transcriptional programs and distinctive biomarkers of progression of T-cell lymphoma. Their role in the aggressive anaplastic lymphoma kinase-negative (ALK–) subtype of anaplastic large cell lymphoma (ALCL) has been elucidated only in part. Starting from our previously identified ALCL-associated lncRNA signature and performing digital gene expression profiling of a retrospective cohort of ALCL, we defined an 11 lncRNA signature able to discriminate among ALCL subtypes. We selected a not previously characterized lncRNA, MTAAT, with preferential expression in ALK– ALCL, for molecular and functional studies. We demonstrated that lncRNA MTAAT contributes to an aberrant mitochondrial turnover restraining mitophagy and promoting cellular proliferation. Functionally, lncRNA MTAAT acts as a repressor of a set of genes related to mitochondrial quality control via chromatin reorganization. Collectively, our work demonstrates the transcriptional role of lncRNA MTAAT in orchestrating a complex transcriptional program sustaining the progression of ALK– ALCL.
