TP53BP2 decreases cell proliferation and induces autophagy in neuroblastoma cell lines

: Tumor protein p53-binding protein 2 (TP53BP2), a member of the apoptosis-stimulating protein of p53 (ASPP) family, has previously been reported to be associated with tumor development. However, to the best of our knowledge, the role of TP53BP2 in neuroblastoma has not been elucidated. The aim of the present study was to investigate the function of TP53BP2 in the proliferation and autophagy of neuroblastoma. An expression vector that expresses TP53BP2-specific short hairpin RNA (shTP53BP2) was used for the experimental group and green fluorescent protein short hairpin RNA was used as a control. Cell proliferation was measured using MTT assays, self-renewal was evaluated using soft agar assays, light chain 3 (LC3) II expression level was examined by western blot and immunofluorescence analysis, and the autophagy-related 3 homolog (ATG3), autophagy-related 5 homolog (ATG5) and autophagy-related 9 homolog (ATG7) expression levels were examined using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A genomics analysis revealed that TP53BP2 expression was associated with the survival of patients with neuroblastoma. Western blot and RT-qPCR assays indicated that TP53BP2 could be implicated in neuroblastoma, as the proliferative ability of the experimental group decreased compared with that of the control group (P<0.001) and the expression levels of genes associated with autophagy, including LC3 II. ATG3, ATG5 and ATG7, increased in the experimental group. In conclusion, an increased expression of TP53BP2 in patients with neuroblastoma may be associated with poor survival and shTP53BP2 may decrease the proliferative abilities of neuroblastoma cells, including BE(2)C and SK-N-DZ cell lines. In addition, the LC3 II, ATG3, ATG5 and ATG7 expression levels increased and were associated with increased rates of autophagy following upregulation of TP53BP2.