No 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.

The targeting protein for Xenopus kinesin-like protein 2 (TPX2) is associated with the metastasis and prognosis of bladder cancer. p53 is closely related to the progression of bladder cancer. Human glioma pathogenesis-related protein 1 (GLIPR1) is a p53 target gene with antitumor activity. This study aims to explore the interplay between TPX2, p53, and GLIPR1 and its correlation with cell proliferation, invasion, and tumor growth in bladder cancer. Here, Western blot and qRT-PCR analysis revealed that TPX2 at both mRNA and protein levels was up-regulated in bladder carcinoma tissues compared to their paired adjacent normal tissues. Additionally, tissues expressing high TPX2 level exhibited high p53 level and low GLIPR1 level. The expressions of TPX2 and p53 in non-muscle-invasive bladder cancer cells (KK47 and RT4) were lower than those in muscle-invasive bladder cancer cells (T24, 5637, and UM-UC-3), while GLIPR1 showed the converse expression pattern. Further investigation revealed that TPX2 activated the synthesis of p53; and GLIPR1 is up-regulated by wild-type (wt)-p53 but not affected by mutated p53; Additionally, GLIPR1 inhibited TPX2. These data suggested a TPX2-p53-GLIPR1 regulatory circuitry. Meanwhile, TPX2 overexpression promoted while overexpression of GLIPR1 or p53 inhibited bladder cancer growth. Interestingly, in T24 cells with mutated p53, p53 silence suppressed bladder cancer growth. This study identified a novel TPX2-p53-GLIPR1 regulatory circuitry which modulated cell proliferation, migration, invasion, and tumorigenicity of bladder cancer. Our findings provide new insight into underlying mechanisms of tumorigenesis and novel therapeutic options in bladder cancer.

Aberrantly expressed microRNAs (miRs) are extensively involved in tumorigenesis. microRNA-340 (miR-340) has been reported as a tumor suppressor in various cancer types. However, whether miR-340 plays an important role in prostate cancer remains unknown. This study aims to investigate the expression pattern of miR-340 and its functional significance in prostate cancer. Results showed that miR-340 expression was frequently downregulated in human prostate cancer cell lines and cancer tissues. miR-340 overexpression suppressed proliferative and invasive properties of prostate cancer cells. This overexpression also promoted prostate cancer cell apoptosis. Conversely, miR-340 silencing showed an opposite effect. Intriguingly, on the basis of bioinformatics analysis and luciferase reporter assay, we found that miR-340 directly targeted the 3'-untranslated region of the high-mobility group nucleosome-binding domain 5 (HMGN5). Quantitative polymerase chain reaction and western blot analysis further verified the results and demonstrated that miR-340 regulated HMGN5 expression. Correlation analysis also showed that HMGN5 expression levels were significantly inversely correlated with the miR-340 expression in prostate cancer tissues. Furthermore, miR-340 overexpression significantly decreased the protein expression of cyclin B1, Bcl-2, and matrix metalloproteinase-9, which are critical regulators for maintaining tumorigenic potential of cancer cells. In addition, overexpression of HMGN5 significantly reversed the inhibitory effect of miR-340 on prostate cancer cell proliferation and invasion. In summary, this study suggests that miR-340 suppresses the tumorigenic potential of prostate cancer cells. Moreover, the decreased miR-340 expression may contribute to the development and progression of prostate cancer through a mechanism that involves HMGN5. Thus, miR340 and its target gene HMGN5 can serve as potentially useful therapeutic candidates for prostate cancer treatment.

Laparoscopic extravascular stent placement appears feasible and safe and it is a minimally invasive alternative to open surgery.