Investigating miR-9 and miR-222 in CSF and Plasma of Neuroblastoma Patients as Metastatic and Apoptotic-Related Markers.

Neuroblastoma is a cancer that occurs due to abnormal development of the sympathetic nervous system. The dysregulation of miR-9 and miR-222 plays a crucial role in neuroblastoma development. These microRNAs have a significant relationship with PTEN, caspase-9, and MMP14, which can potentially form the basis for the specific diagnosis and treatment of this disease. In our study, two neuroblastoma cell lines were divided into three groups based on whether they had been treated with miR-9, anti-miR-9, miR-222, or both. We evaluated various parameters in these groups, including migration (through a wound healing assay), apoptosis (using flow cytometry), and gene expression (through qRT-PCR). Additionally, we measured the expression levels of MMP14, miR-9, and miR-222 in plasma and CSF samples from neuroblastoma patients using ELISA and qRT-PCR. We found that patients with neuroblastoma had higher levels of MMP14 and miR-222 mRNA expression but lower levels of miR-9 mRNA expression. Furthermore, after treating the cell lines with anti-miR-9 and anti-miR-222, we observed increased levels of MMP14 expression, as well as PTEN and caspase-9. Additionally, the treatment with anti-miR-222 and anti-miR-9 led to an increase in the frequency of apoptosis and migration of cancer cells. Our research shows that the dysregulation of miR-9, miR-222, and MMP14 could be key indicators in the pathogenesis of neuroblastoma. We also found that up-regulation of miR-9 was associated with decreased disease severity, whereas up-regulation of miR-222 and MMP14 was linked to increased disease severity.