Long Non-coding RNA NHEG1/hsa-miR-665/HMGB1 Axis is Involved in the Regulation of Neuroblastoma Progression

Long non-coding (lncRNA) neuroblastoma highly expressed 1 (NHEG1) has been reorganized as a prognostic factor in neuroblastoma (NB), but the molecular mechanisms in the suppression of neuroblastoma remain to be elucidated. In our study, we explored the functional roles of lncRNA NHEG1 in neuroblastoma and the underlying molecular mechanism. We collected NB tumor samples and adjacent normal tissues to compare lncRNA NHEG1 expression. Through bioinformatic target prediction, we selected potential downstream effectors of lncRNA NHEG1 for functional validation in NB cell lines. We observed that lncRNA NHEG1 was significantly upregulated in NB tissues as compared to the normal tissues. In NB tissues, lncRNA NHEG1 expression showed an inverse correlation with hsa-miR-665 (miR-655), but a positive correlation with high mobility group box 1 (HMGB1). In NB cell lines, lncRNA NHEG1 knockdown caused the upregulation of miR-665 and the downregulation of HMGB1. Through a series of functional assays, we further demonstrated that lncRNA Nheg1 knockdown suppressed cell proliferation, migration and invasion of NB cells, which could be rescued by miR-665 inhibitor and HMGB1 overexpression. Together, our data demonstrated that lncRNA NHEG1 serves as a competitive partner to negatively regulate the activity of miR-665, which relieves the inhibition on HMGB1 expression and promotes the aggressive phenotype of neuroblastoma cells. Our study indicates that lncRNA NHEG1/miR-665/HMGB1 axis may play an important role in regulating the aggressiveness and the progression of neuroblastoma.