Rab23 is overexpressed in human bladder cancer and promotes cancer cell proliferation and invasion
Rab23 is overexpressed in human bladder cancer and promotes cancer cell proliferation and invasion
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DOI：
10.1007/s13277-015-4590-9
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发表时间：
2016-06-01
期刊：
影响因子：
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通讯作者：
Qiao, Qiao
中科院分区：
文献类型：
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作者：
Jiang, Yuanjun;Han, Yushuang;Qiao, Qiao
Rab 23过表达与几种人类癌症有关。然而，其在人膀胱癌中的表达模式和生物学作用尚未阐明。在这项研究中，我们研究了Rab 23在93例膀胱癌标本中的表达，并分析了其与临床病理参数的相关性。我们发现Rab 23在93个癌标本中的45个（48.3%）中过表达。Rab 23过表达与肿瘤浸润深度之间存在显著相关性（p = 0.0027）。Rab 23过表达与FGFR 3蛋白表达也呈负相关（p = 0.021）。我们发现Rab 23在正常膀胱移行细胞系SV-HUC-1中的表达低于膀胱癌细胞系BIU-87、5637和T24。我们敲低了T24癌细胞中Rab 23的表达，并将Rab 23质粒转染到BIU-87细胞系中。Rab 23缺失抑制细胞生长速率和侵袭，而其过表达导致细胞生长和侵袭增加。此外，我们证明Rab 23耗竭减少，其转染上调细胞周期蛋白E，c-myc和MMP-9的表达。此外，我们发现Rab 23敲低抑制NF-κ B信号传导，而其过表达上调NF-κ B信号传导。BAY 11-7082（NF-κ B抑制剂）部分抑制Rab 23对细胞周期蛋白E和MMP-9表达的影响。总之，本研究表明Rab 23过表达通过NF-κ B B途径促进膀胱癌恶性细胞生长和侵袭。
Rab23 overexpression has been implicated in several human cancers. However, its expression pattern and biological roles in human bladder cancer have not been elucidated. In this study, we examined Rab23 expression in 93 bladder cancer specimens and analyzed its correlation with clinicopathological parameters. We found that Rab23 was overexpressed in 45 of 93 (48.3 %) cancer specimens. Significant association was found between Rab23 overexpression and tumor invasion depth (p = 0.0027). Rab23 overexpression also negatively correlated with FGFR3 protein expression (p = 0.021). We found that Rab23 expression was lower in normal bladder transitional cell line SV-HUC-1 than in bladder cancer cell lines BIU-87, 5637, and T24. We knocked down Rab23 expression in T24 cancer cells and transfected a Rab23 plasmid in the BIU-87 cell line. Rab23 depletion inhibited cell growth rate and invasion, while its overexpression resulted in increased cell growth and invasion. In addition, we demonstrated that Rab23 depletion decreased and its transfection upregulated expression of cyclin E, c-myc, and MMP-9. Furthermore, we showed that Rab23 knockdown inhibited NF-kappa B signaling and its overexpression upregulated NF-kappa B signaling. BAY 11-7082 (NF-kappa B inhibitor) partly inhibited the effect of Rab23 on cyclin E and MMP-9 expression. In conclusion, the present study demonstrated that Rab23 overexpression facilitates malignant cell growth and invasion in bladder cancer through the NF-kappa B pathway.