LncRNA NORAD accelerates the progression and doxorubicin resistance of neuroblastoma through up-regulating HDAC8 via sponging miR-144-3p

The dysregulation of non-coding RNAs (ncRNAs) often caused aberrant cell behaviors. In the present study, we focused on the role of long noncoding RNA (lncRNA) non-coding RNA activated by DNA damage (NORAD) in the development of neuroblastoma (NB). The enrichment of NORAD, miRNA-144-3p (miR-144-3p) and histone deacetylase 8 (HDAC8) was measured by quantitative real time polymerase chain reaction (qRT-PCR). The proliferation, chemoresistance, apoptosis, metastasis and autophagy of NB cells were determined by 344,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, transwell migration and invasion assays and Western blot assay, respectively. The target relationship between miR-144-3p and NORAD or HDAC8 was predicted by Starbase software and validated through dual-luciferase reporter assay, RIP and RNA-pull down assays. The protein expression of HDAC8 was measured by Western blot assay. Murine xenograft model was used to verify the function of NORAD in vivo. We found that the level of NORAD was up-regulated in NB tissues and cells, and the level of NORAD was negatively correlated with the prognosis of NB patients. NORAD promoted the proliferation, metastasis and doxorubicin (DOX) resistance while inhibited the apoptosis and autophagy of NB cells. MiR-144-3p was a target of NORAD in NB cells, and NORAD accelerated the progression and DOX resistance of NB through sponging miR-144-3p. HDAC8 was a direct target of miR-144-3p in NB cells, and miR-144-3p suppressed the progression of NB through down-regulating HDAC8. NORAD upregulated the expression of HDAC8 through sponging miR-144-3p in NB cells. NORAD accelerated the growth of NB tumors at least partly through miR-144-3p/HDAC8 signaling in vivo. In conclusion, NORAD promoted the progression and DOX resistance of NB through miR-144-3p/HDAC8 axis in vivo and in vitro.