Identifying miRNAs as predictive markers of good prognosis in neuroblastoma

Neuroblastoma (NB) is the most common extracranial tumor in children. NB has a wide range of outcomes, from good to poor prognosis. Currently, there are no reliable predictive markers to assess favorable prognosis in NB. Recent studies have explored the relationship between NB and microRNAs (miRNAs), with several reports suggesting that miRNA expression may serve as prognostic markers for NB.

We performed miRNA array analysis using serum samples at the time of diagnosis from 12 patients with NB treated at our hospital, with six patients in each of the high- and low-risk groups, according to the International Neuroblastoma Risk Group Staging (INRG). NB cell lines were treated with retinoic acid and differentiated. We assessed the role of miRNAs by measuring their expression in exosomes and introducing miRNA mimics into NB cell lines.

The miRNA array identified four miRNAs-miR-4716-5p, miR-4305, miR-4285, and miR-3692*-as promising candidate markers for low-risk NB. Following treatment of NB cell lines with 10 μM RA, neuron-like morphological changes, including neurite outgrowth, were observed, along with increased expression of the four miRNAs in the culture medium of all NB cell lines. Furthermore, the concentration of exosomes and the levels of the four miRNAs in exosomes were increased during NB cell line differentiation. The introduction of miRNA mimics into SH-SY5Y cells led to elevated expression of neurofilament heavy and medium chains.

The four miRNAs are markers of good prognosis, could be involved in neuronal differentiation, and may be used as a therapeutic assessment tool for NB.