Bioinformatics analysis of miRNAs in the neuroblastoma 11q-deleted region reveals a role of miR-548l in both 11q-deleted and MYCN amplified tumour cells

Neuroblastoma is a childhood tumour that is responsible for approximately 15% of all childhood cancer deaths. Neuroblastoma tumours with amplification of the oncogene MYCN are aggressive, however, another aggressive subgroup without MYCN amplification also exists; rather, they have a deleted region at chromosome arm 11q. Twenty-six miRNAs are located within the breakpoint region of chromosome 11q and have been checked for a possible involvement in development of neuroblastoma due to the genomic alteration. Target genes of these miRNAs are involved in pathways associated with cancer, including proliferation, apoptosis and DNA repair. We could show that miR-548l found within the 11q region is downregulated in neuroblastoma cell lines with 11q deletion or MYCN amplification. In addition, we showed that the restoration of miR-548l level in a neuroblastoma cell line led to a decreased proliferation of these cells as well as a decrease in the percentage of cells in the S phase. We also found that miR-548l overexpression suppressed cell viability and promoted apoptosis, while miR-548l knockdown promoted cell viability and inhibited apoptosis in neuroblastoma cells. Our results indicate that 11q-deleted neuroblastoma and MYCN amplified neuroblastoma coalesce by downregulating miR-548l.

Automated summary

Neuroblastoma is a childhood tumor that is responsible for a significant proportion of childhood cancer deaths. Two aggressive subgroups of neuroblastoma, one with amplification of the oncogene MYCN and the other with a deletion at chromosome arm 11q, have been identified. In this study, researchers focused on 26 miRNAs located within the 11q breakpoint region and found that they may play a role in the development of neuroblastoma. The target genes of these miRNAs are involved in important cancer-related pathways. Specifically, they found that miR-548l, which is downregulated in neuroblastoma cell lines with 11q deletion or MYCN amplification, plays a role in cell proliferation, apoptosis, and DNA repair. Restoring the level of miR-548l in neuroblastoma cells led to decreased cell proliferation and cell cycle progression, as well as increased apoptosis.