Mitotic spindle organizing protein 2A (MZT2A) promotes NSCLC cell viability and invasion by upregulating galectin-3-binding protein (LGALS3BP), increases AKT phosphorylation via the MOZART2 domain and predicts poor NSCLC prognosis

Abstract Background : Mitotic spindle organizing protein 2A (MZT2A) is localized at the centrosome and regulates microtubule nucleation activity in cells. This study assessed the role of MZT2A in non-small cell lung cancer (NSCLC). Methods : Differential MZT2A expression was bioinformatically assessed using the Cancer Genome Atlas database, Gene Expression Profiling Interactive Analysis database, and Kaplan-Meier survival data to determine the association between MZT2A expression and NSCLC prognosis. Furthermore, NSCLC tissue specimens from 132 patients were evaluated with immunohistochemistry. MZT2A was overexpressed or knocked down in NSCLC cells using cDNA and siRNA, respectively. The cells were subjected to various assays and treated with the selective Akt inhibitor LY294002 or co-transfected with galectin-3-binding protein (LGALS3BP) siRNA. Result : The levels of MZT2A mRNA and protein were upregulated in NSCLC lesions and MTZ2A expression was associated with larger tumor size, lymph node metastasis, and advanced TNM stages for NSCLC as well as poor NSCLC prognosis. MZT2A protein was also highly expressed in NSCLC cells compared to the expression in normal bronchial cells. MZT2A expression promoted NSCLC cell viability and invasion, whereas MTZ2A siRNA had the opposite effects on NSCLC cells in vitro. At the protein level, MZT2A induced Akt phosphorylation, promoting NSCLC proliferation and invasion (but the selective Akt inhibitor blocked these effects) through the upregulation of LGALS3BP via the MTZ2A MOZART2 domain, whereas LGALS3BP siRNA suppressed MTZ2A activity in NSCLC cells. Conclusions : MZT2A exhibits oncogenic activity by activating LGALS3BP and Akt in NSCLC. Future studies will assess MTZ2A as a biomarker to predict NSCLC prognosis or as a target to control NSCLC progression.