Objectives: Bladder cancer (BC) is a common malignancy worldwide. Signal peptidase complex 18 (SPC18) protein, which is encoded by the SEC11A gene, is one of the subunits of the signal peptidase complex and induces transforming growth factor-α secretion. In the present study, we analyzed the expression and function of SPC18 protein in human BC. Methods: Expression of SPC18 was analyzed by immunohistochemistry. RNA interference was used to inhibit SEC11A expression in BC cell lines. For constitutive expression of the SEC11A gene, a SEC11A expression vector was transfected into BC cell lines. To examine cell viability, we performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Modified Boyden chamber assays were used to examine cell invasiveness. Results: SPC18 was upregulated in 54% of 81 BC cases. SPC18 expression served as an independent prognostic classifier of patients with BC. SPC18-positive BC cases frequently expressed cytokeratin 5/6, a marker of basal-like BC. Cell growth and invasiveness were inhibited by SEC11A knockdown and enhanced by forced expression of SEC11A. Conclusion: These results indicate that SPC18 plays an important role in the progression of BC. Specific inhibitors of SPC18 may be promising anticancer drugs for patients with basal-like BC.

中文翻译：

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SEC11A表达与基底样膀胱癌相关并预测患者存活率

目的：膀胱癌（BC）是世界范围内常见的恶性肿瘤。信号肽酶复合物 18 (SPC18) 蛋白由 SEC11A 基因编码，是信号肽酶复合物的亚基之一，可诱导转化生长因子-α 分泌。在本研究中，我们分析了 SPC18 蛋白在人类 BC 中的表达和功能。方法：免疫组化分析SPC18的表达。RNA干扰用于抑制BC细胞系中的SEC11A表达。对于 SEC11A 基因的组成型表达，将 SEC11A 表达载体转染到 BC 细胞系中。为了检查细胞活力，我们进行了 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 测定。使用改良的 Boyden 室测定来检查细胞侵袭性。结果：SPC18 在 81 例 BC 病例中的 54% 上调。SPC18 表达作为 BC 患者的独立预后分类器。SPC18 阳性 BC 病例经常表达细胞角蛋白 5/6，这是基底样 BC 的标志物。细胞生长和侵袭性被 SEC11A 敲低抑制，并通过 SEC11A 的强制表达而增强。结论：这些结果表明 SPC18 在 BC 的进展中起重要作用。SPC18 的特异性抑制剂可能是用于基底样 BC 患者的有希望的抗癌药物。