Bladder cancer (BCa) is a common malignancy in the urinary system. Ras-related protein Rab-27A (RAB27A) and Ras-related protein Rab-27B (RAB27B) have been verified to be closely related to the development of many tumors. Since the role of both RAB27A and RAB27B in BCa have not been reported, we intended to explore the function and mechanism of RAB27A and RAB27B in BCa development. Reverse transcription quantitative polymerase chain reaction revealed that RAB27A/B showed high expression in BCa tissues and cells. Cell counting kit-8, wound healing and Transwell assays as well as western blot analyses revealed that silencing RAB27A/B suppressed BCa cell proliferation, migration and invasion as well as the epithelial-mesenchymal transition (EMT) process. Based on bioinformatics analysis and our experiments, microRNA-186-5p (miR-186-5p) was found to be the upstream miRNA of RAB27A/B in BCa. MiR-186-5p expression was significantly downregulated in BCa cells and tissues. MiR-186-5p directly targeted the 3′-untranslated region (3′-UTR) of RAB27A/B and downregulated both mRNA and protein levels of RAB27A/B in BCa cells. MiR-186-5p overexpression suppressed BCa cell proliferation, migration and invasion as well as the EMT process in vitro and inhibited tumor growth in vivo. Overexpressing RAB27A/B rescued the inhibitory effect of miR-186-5p on malignant phenotypes of BCa cells. Furthermore, miR-186-5p inactivated the phosphatidylinositol 3-Kinase (PI3K)/mitogen-activated protein kinase (MAPK) signaling pathway by downregulating the expression of RAB27A/B, as shown in western blot analysis. Overall, miR-186-5p suppressed BCa cell proliferation, migration, invasion and EMT process and inhibited xenograft tumor growth by targeting RAB27A/B to inactivate the PI3K/MAPK signaling.

中文翻译：

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MiR-186-5p 通过靶向 RAB27A/B 抑制膀胱癌细胞迁移、侵袭和上皮间质转化

膀胱癌 (BCa) 是泌尿系统中常见的恶性肿瘤。Ras相关蛋白Rab-27A（RAB27A）和Ras相关蛋白Rab-27B（RAB27B）已被证实与多种肿瘤的发生发展密切相关。由于 RAB27A 和 RAB27B 在 BCa 中的作用尚未见报道，我们拟探讨 RAB27A 和 RAB27B 在 BCa 发展中的功能和机制。逆转录定量聚合酶链反应显示RAB27A/B在BCa组织和细胞中呈高表达。细胞计数试剂盒 8、伤口愈合和 Transwell 测定以及蛋白质印迹分析表明，沉默 RAB27A/B 抑制了 BCa 细胞增殖、迁移和侵袭以及上皮-间质转化 (EMT) 过程。基于生物信息学分析和我们的实验，microRNA-186-5p (miR-186-5p)被发现是BCa中RAB27A/B的上游miRNA。MiR-186-5p 表达在 BCa 细胞和组织中显着下调。MiR-186-5p 直接靶向 RAB27A/B 的 3'-非翻译区 (3'-UTR)，下调 BCa 细胞中 RAB27A/B 的 mRNA 和蛋白水平。MiR-186-5p 过表达在体外抑制了 BCa 细胞增殖、迁移和侵袭以及 EMT 过程，并在体内抑制了肿瘤生长。过表达 RAB27A/B 可以挽救 miR-186-5p 对 BCa 细胞恶性表型的抑制作用。此外，miR-186-5p 通过下调 RAB27A/B 的表达使磷脂酰肌醇 3-激酶 (PI3K)/丝裂原活化蛋白激酶 (MAPK) 信号通路失活，如蛋白质印迹分析所示。总体而言，miR-186-5p 抑制了 BCa 细胞增殖、迁移、