MicroRNA-451 inhibits neuroblastoma proliferation, invasion and migration by targeting macrophage migration inhibitory factor

Abstract

Neuroblastoma (NB) is the most prevalent type of extracranial solid tumour in young children. To improve current understanding of the mechanisms, which modulate cancer cell proliferation, invasion and migration, investigations have focused on microRNAs (miRs), a class of small non‑coding RNAs, which post‑transcriptionally regulate gene expression during various crucial cell processes. The present study aimed to investigate the role of miR‑451 in NB. Human NB tissue and adjacent normal tissue were surgically removed, and the expression of miR‑451, and development and pathological characteristics of NB were investigated. The expression of miR‑451 was reduced in the NB tissue, compared with that in the adjacent tissue, and correlations between the reduction in miR‑451 and unfavourable variables included tumour size (P=0.0081), differentiation (P=0.0217), lymph node metastasis (P=0.0489), tumour‑node‑metastasis stage (0.0220) and distant metastases (P=0.0201). Transfection of the SK‑N‑SH and GI‑LA‑N NB cell lines with miR‑451 inhibited cell growth, invasion and migration. Furthermore, the present study demonstrated that macrophage migration inhibitory factor (MIF) was regulated directly by miR‑451 and was a critical mediator of the biological effects of miR‑451 in NB. The re‑expression of MIF markedly reversed the carcinogenic inhibitory property of miR‑451. These data provide a more detailed understanding of the essential role of miR‑451 in NB, which relies on regulation of the expression of MIF.

microRNA and Overcoming the Challenges of Their Use in the Diagnosis of Endometriosis

“…Both prior studies employed RNU6 as a reference. While hsa-miR-451a has been found to act as a tumor suppressor [64,65], it is also a marker of hemolysis [66] and thus we suggest that care should be employed to exclude samples with hemolysis before analysis. The miRNA ratio of hsa-miR-451a and hsa-miR-23a-3p has been employed by others [56,67] to monitor for sample hemolysis.…”

Emerging Role of the Macrophage Migration Inhibitory Factor Family of Cytokines in Neuroblastoma. Pathogenic Effectors and Novel Therapeutic Targets?

“…Liu et al have shown that the transfection of the SK-N-SH and GI-LA-N human NB cell lines with miR-451 reduced tumor proliferation, invasion, and migration, and that MIF was negatively regulated by miR-451 that directly targeted the 3 UTR of MIF mRNA in the NB cell lines [99]. Moreover, the overexpression of MIF counteracted the inhibitory action of miR-451 on NB cells growth, invasiveness, and migration, thus indicating that the anticancer activity of miR-451 may be due to the suppression of MIF expression [99].…”

“…Liu et al have shown that MIF was a direct target gene of miR-451, which was significantly downregulated in tumor tissue samples of NB patients [99]. Moreover, they found that the reduction in miR-451 was significantly associated with negative tumor features, such as higher TNM stage, larger carcinoma size, lower degree of differentiation, and higher presence of metastases [99]. Therefore, they suggested that the miR-451/MIF pathway could be a novel therapeutic target for NB patients [99].…”

Molecular Events Controlling Cessation of Trunk Neural Crest Migration and Onset of Differentiation

“…One hypothesis we would like to present is that expression of MIF in the migrating tNCC might favor DRG ganglionation via self-attraction. MIF is highly overexpressed in many types of malignant tumors and its level of upregulation has been correlated with the aggressiveness of the cancers (Chesney and Mitchell, 2015;Liu et al, 2016). Interestingly, neuroblastomas, which are of NCC origin, express high level of MIF (Zhou et al, 2008).…”