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A context-dependent role for MiR-124-3p on cell phenotype, viability and chemosensitivity in neuroblastoma in vitro.

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posted on 26.03.2021, 13:35 by John Nolan, Manuela Salvucci, Steven Carberry, Ana Barat, Miguel F Segura, Justine Fenn, Jochen Prehn, Raymond Stallings, Olga Piskareva
Neuroblastoma (NB) is a neural crest-derived tumor, which develops before birth or in early childhood, with metastatic dissemination typically preceding diagnosis. Tumors are characterized by a highly heterogeneous combination of cellular phenotypes demonstrating varying degrees of differentiation along different lineage pathways, and possessing distinct super-enhancers and core regulatory circuits, thereby leading to highly varied malignant potential and divergent clinical outcomes. Cytoskeletal reorganization is fundamental to cellular transformations, including the processes of cellular differentiation and epithelial to mesenchymal transition (EMT), previously reported by our lab and others to coincide with chemotherapy resistance and enhanced metastatic ability of tumor cells. This study set out to investigate the ability of the neuronal miR-124-3p to reverse the cellular transformation associated with drug resistance development and assess the anti-oncogenic role of this miRNA in in vitro models of drug-resistant adrenergic (ADRN) and mesenchymal (MES) neuroblastoma cell lines. Low expression of miR-124-3p in a cohort of neuroblastomas was significantly associated with poor overall and progression-free patient survival. Over-expression of miR-124-3p in vitro inhibited cell viability through the promotion of cell cycle arrest and induction of apoptosis in addition to sensitizing drug-resistant cells to chemotherapeutics in a panel of morphologically distinct neuroblastoma cell lines. Finally, we describe miR-124-3p direct targeting and repression of key up-regulated cytoskeletal genes including MYH9, ACTN4 and PLEC and the reversal of the resistance-associated EMT and enhanced invasive capacity previously reported in our in vitro model (SK-N-ASCis24).

Funding

National Children’s Research Centre (Project grant A/17/2)

Science Foundation Ireland (13/IA/1881 and 14/IA/2582)

History

Associated research data files

Supplementary material (including datasets locations) can be found at doi.org/10.3389/fcell.2020.559553

Comments

The original article is available at https://www.frontiersin.org

Published Citation

Nolan JC, Salvucci M, Carberry S, Barat A, Segura MF, Fenn J, Prehn JHM, Stallings RL, Piskareva O. A context-dependent role for MiR-124-3p on cell phenotype, viability and chemosensitivity in neuroblastoma in vitro. Frontiers in Cell and Developmental Biology.2020;8:559553.

Publication Date

20 November 2020

PubMed ID

33330445

Department/Unit

  • Anatomy and Regenerative Medicine
  • Physiology and Medical Physics
  • School of Pharmacy and Biomolecular Sciences
  • Centre for Systems Medicine

Research Area

  • Cancer
  • Biomaterials and Regenerative Medicine
  • Immunity, Infection and Inflammation

Publisher

Frontiers Media SA

Version

  • Published Version (Version of Record)

Licence

Exports

Royal College of Surgeons in Ireland

Licence

Exports