miR-22 suppresses DNA ligase III addiction in multiple myeloma

Daniele Caracciolo, Maria Teresa Di Martino, Nicola Amodio, Eugenio Morelli, Martina Montesano, Cirino Botta, Francesca Scionti, Daniela Talarico, Emanuela Altomare, Maria Eugenia Gallo Cantafio, Valeria Zuccalà, Lorenza Maltese, Katia Todoerti, Marco Rossi, Mariamena Arbitrio, Antonino Neri, Pierosandro Tagliaferri, Pierfrancesco Tassone

Research output: Contribution to journalArticle

Abstract

Multiple myeloma (MM) is a hematologic malignancy characterized by high genomic instability. Here we provide evidence that hyper-activation of DNA ligase III (LIG3) is crucial for genomic instability and survival of MM cells. LIG3 mRNA expression in MM patients correlates with shorter survival and even increases with more advanced stage of disease. Knockdown of LIG3 impairs MM cells viability in vitro and in vivo, suggesting that neoplastic plasmacells are dependent on LIG3-driven repair. To investigate the mechanisms involved in LIG3 expression, we investigated the post-transcriptional regulation. We identified miR-22-3p as effective negative regulator of LIG3 in MM. Enforced expression of miR-22 in MM cells downregulated LIG3 protein, which in turn increased DNA damage inhibiting in vitro and in vivo cell growth. Taken together, our findings demonstrate that myeloma cells are addicted to LIG3, which can be effectively inhibited by miR-22, promoting a novel axis of genome stability regulation.

Original languageEnglish
Pages (from-to)487-498
JournalLeukemia
Volume33
Issue number2
DOIs
Publication statusPublished - 2019

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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  • Cite this

    Caracciolo, D., Di Martino, M. T., Amodio, N., Morelli, E., Montesano, M., Botta, C., Scionti, F., Talarico, D., Altomare, E., Gallo Cantafio, M. E., Zuccalà, V., Maltese, L., Todoerti, K., Rossi, M., Arbitrio, M., Neri, A., Tagliaferri, P., & Tassone, P. (2019). miR-22 suppresses DNA ligase III addiction in multiple myeloma. Leukemia, 33(2), 487-498. https://doi.org/10.1038/s41375-018-0238-2