Target protein for Xklp2 (TPX2), a microtubule-related protein, contributes to malignant phenotype in bladder carcinoma

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Abstract
Increasing evidence demonstrated that TPX2 was highly expressed and tightly associated with human tumor development and progression. However, its precise role in bladder carcinoma remains to be delineated. In the present study, we revealed the high expression of TPX2 at both mRNA and protein levels in bladder carcinoma tissues and cells, and TPX2 levels in pN1-3 and pT2-4 status were significantly higher than those in pN0 and pTa-T1 status, respectively. Additionally, high TPX2 level was strongly associated with pT status (P = 0.001), higher histological grade (P = 0.001), lymph node metastasis (P = 0.022), and shorter survival time (P = 0.0279). Further investigation showed that TPX2 level in T24 cells was markedly higher than those in 5637, J82 and RT4 cells, in which RT4, a well-differentiated cell line derived from bladder carcinoma with low-grade non-invasive T0, displayed the lowest TPX2 mRNA and protein levels. Besides, TPX2 overexpression promoted proliferation and tumorigenicity, shortened cell cycle in G0/G1 phase, and suppressed cell apoptosis in T24 cells; conversely, TPX2 depletion exhibited opposite effects. Furthermore, TPX2 overexpression evoked the elevation of cyclin D1 and cdk2 levels as well as reduction of p21 level and caspase-3 activity, whereas reversed effects were observed in TPX2-depleted T24 cells. Taken altogether, TPX2 may play a central role in the development and progression of bladder carcinoma, and thus inhibition of TPX2 level may be a novel strategy for therapy of the patients with bladder carcinoma.

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