Articolo in rivista, 2021, ENG, 10.3390/cancers13010015

Metabolic reprogramming by malat1 depletion in prostate cancer

Nanni, Simona; Aiello, Aurora; Salis, Chiara; Re, Agnese; Cencioni, Chiara; Bacci, Lorenza; Pierconti, Francesco; Pinto, Francesco; Ripoli, Cristian; Ostano, Paola; Baroni, Silvia; Lazzarino, Giacomo; Tavazzi, Barbara; Pugliese, Dario; Bassi, Pierfrancesco; Grassi, Claudio; Panunzi, Simona; Chiorino, Giovanna; Pontecorvi, Alfredo; Gaetano, Carlo; Farsetti, Antonella

UniCamillus - Saint Camillus International University of Health and Medical Sciences; Istituti Clinici Scientifici Maugeri Spa - SB; Fondazione Edo ed Elvo Tempia; Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Università Cattolica del Sacro Cuore, Campus di Roma; Consiglio Nazionale delle Ricerche

The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) promotes growth and progression in prostate cancer (PCa); however, little is known about its possible impact in PCa metabolism. The aim of this work has been the assessment of the metabolic reprogramming associated with MALAT1 silencing in human PCa cells and in an ex vivo model of organotypic slice cultures (OSCs). Cultured cells and OSCs derived from primary tumors were transfected with MALAT1 specific gapmers. Cell growth and survival, gene profiling, and evaluation of targeted metabolites and metabolic enzymes were assessed. Computational analysis was made considering expression changes occurring in metabolic markers following MALAT1 targeting in cultured OSCs. MALAT1 silencing reduced expression of some metabolic enzymes, including malic enzyme 3, pyruvate dehydrogenase kinases 1 and 3, and choline kinase A. Consequently, PCa metabolism switched toward a glycolytic phenotype characterized by increased lactate production paralleled by growth arrest and cell death. Conversely, the function of mitochondrial succinate dehydrogenase and the expression of oxidative phosphorylation enzymes were markedly reduced. A similar effect was observed in OSCs. Based on this, a predictive algorithm was developed aimed to predict tumor recurrence in a subset of patients. MALAT1 targeting by gapmer delivery restored normal metabolic energy pathway in PCa cells and OSCs.

Cancers (Basel) 13 (1), pp. 1–29

Keywords

Biomarkers, Long noncoding RNA, MALAT1, Metabolic reprogramming, Metabolism, Precision medicine, Predictive model, Prostate cancer, Transcription

CNR authors

Farsetti Antonella, Cencioni Chiara

CNR institutes

IASI – Istituto di analisi dei sistemi ed informatica "Antonio Ruberti"