Long non-coding RNA mitophagy and ALK-negative anaplastic lymphoma-associated transcript: a novel regulator of mitophagy in T-cell lymphoma

Haematologica. 2023 Dec 1;108(12):3333-3346. doi: 10.3324/haematol.2022.282552.

Abstract

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.

MeSH terms

  • Anaplastic Lymphoma Kinase / genetics
  • Humans
  • Lymphoma, Large-Cell, Anaplastic* / pathology
  • Lymphoma, T-Cell, Peripheral*
  • Mitophagy / genetics
  • RNA, Long Noncoding* / genetics
  • Receptor Protein-Tyrosine Kinases / genetics
  • Retrospective Studies

Substances

  • Receptor Protein-Tyrosine Kinases
  • Anaplastic Lymphoma Kinase
  • RNA, Long Noncoding

Grants and funding

Funding: VM and AT were supported by Fondazione AIRC per la Ricerca sul Cancro (AIRC). FR was supported by Fondazione Umberto Veronesi. VM and AR were supported by Fondazione GRADE Onlus. This study was funded by the Italian Ministry of Health through Ricerca Finalizzata (N. GR-2016-02364298, to VF), Bando per la Valorizzazione della Ricerca Istituzionale 2021- fondi 5 per Mille 2020 (to VF) and Fondazione AIACE (to VF). The study was also partially supported by the Italian Ministry of Health-Ricerca Corrente Annual Program 2024.