Urothelial bladder cancer (BCa) is a common malignant tumor of the urinary system. It has been identified that exosomal miRNAs contribute to the development of BCa. However, its significance and mechanism in the malignant biological behavior of BCa remain unclear. In this study, the influence of exosomal miRNAs on BCa progression was investigated. High-throughput sequencing was conducted to analyze the microRNA-expression profile in urinary exosomes to screen out the key miRNA of muscle-invasive bladder cancer (MIBC). Then, candidate miRNA expression was verified and validated in urinary exosomes and tissue samples. To address the potential role of the candidate miRNA, we overexpressed and knocked down the candidate miRNA and explored its activity in BCa cell lines. Furthermore, the target gene of the selected miRNA was predicted and validated. The expression profile of miRNAs revealed increased expression of miR-17-5p in MIBC urinary exosomes, and this was later confirmed in urinary exosomes and tissue samples. Cell function studies revealed that exosomal miR-17-5p significantly promoted the growth and invasion of BCa cells. Bioinformatics and luciferase experiments demonstrated that the ARID4B mRNA 3′ UTR might be the binding site for miR-17-5p. Low ARID4B levels were linked to high-grade BCa patients and were associated with a better prognosis. Elevated miR-17-5p contributes to BCa progression by targeting ARID4B and influencing the immune system. Based on these findings, miR-17-5p has the potential to be a new therapeutic target for the treatment of BCa.

中文翻译：

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尿外泌体 miR-17-5p 通过抑制靶基因 ARID4B 和调节免疫微环境加速膀胱癌侵袭

膀胱尿路上皮癌（BCa）是泌尿系统常见的恶性肿瘤。已经确定外泌体 miRNA 有助于 BCa 的发育。然而，其在BCa恶性生物学行为中的意义和机制仍不清楚。在本研究中，研究了外泌体 miRNA 对 BCa 进展的影响。通过高通量测序分析尿液外泌体中的 microRNA 表达谱，筛选出肌层浸润性膀胱癌 (MIBC) 的关键 miRNA。然后，在尿液外泌体和组织样本中验证和确认候选 miRNA 的表达。为了解决候选 miRNA 的潜在作用，我们过表达并敲低候选 miRNA，并探索其在 BCa 细胞系中的活性。此外，还对所选miRNA的靶基因进行了预测和验证。 miRNA 的表达谱显示 MIBC 尿液外泌体中 miR-17-5p 的表达增加，这一点后来在尿液外泌体和组织样本中得到证实。细胞功能研究表明，外泌体miR-17-5p显着促进BCa细胞的生长和侵袭。生物信息学和荧光素酶实验证明ARID4B mRNA 3'UTR可能是miR-17-5p的结合位点。低 ARID4B 水平与高级别 BCa 患者相关，并且与更好的预后相关。 miR-17-5p 升高通过靶向 ARID4B 并影响免疫系统，促进 BCa 进展。基于这些发现，miR-17-5p有潜力成为治疗BCa的新治疗靶点。