iASPP overexpression is associated with clinical outcome in spinal chordoma and influences cellular proliferation, invasion, and sensitivity to cisplatin in vitro.

ABSTRACT

The oncogenetic function of inhibitory member of the apoptosis stimulating protein of p53 family (iASPP) in chordoma is unclear and remains to elucidate. The expression of iASPP in chordoma tissues and cells, its correlation to clinicopathological parameters and the effect on the patients' prognosis were evaluated. Cellular proliferation, invasion and cisplatin-response were observed after the iASPP knockdown or overexpression in vitro. Co-Immunoprecipitation assay was used to explore the interaction between iASPP and p53. The regulation of miRNA-124 on the expression and apoptotic function of iASPP was explored after transiently transfecting cells with miRNA-124 mimics or inhibitor. Results indicated that iASPP overexpressed in chordoma tissues and cells. Its overexpression was associated with tumor invasion and local recurrence, and was predictive of patients' poor prognosis. Cells with iASPP-silence showed a decreased ability of proliferation and invasion, but an increasing sensitivity to cisplatin. Besides, iASPP could combine with p53 in either endogenous or exogenous detection. Post-transcriptionally, miRNA-124 negatively regulated the expression of iASPP, which further led to the changes of apoptosis-related proteins. Thus, iASPP overexpression is associated with the clinical outcome in spinal chordoma and influences cellular proliferation, invasion, and the sensitivity to cisplatin.