MiR-4644 is upregulated in plasma exosomes of bladder cancer patients and promotes bladder cancer progression by targeting UBIAD1

摘要

Exosome-encapsulated microRNAs (miRNAs) have been identified as potential cancer biomarkers and pro-tumorigenic mediators for several cancers. However, the miRNA profiling in BCa-Exo (exosomes from plasma of patients with bladder cancer) has not yet been explored. Hence, the aim of this study was to analyze the miRNA profiling in BCa-Exo and to explore the function and mechanism of the selected miR-4644 in BCa progression. Of the 8 differentially expressed miRNAs in BCa-Exo relative to NC-Exo (exosomes from plasma of normal control subjects), hsa-miR-4644 was the only upregulated (fold change 2.0, P 0.05) miRNA, which was further confirmed to be upregulated in plasma of BCa patients and BCa cell lines. Further in vitro assays demonstrated that miR-4644 mimic promoted, whereas miR-4644 inhibitor suppressed BCa cell proliferation and invasion. miR-4644 negatively regulated expression of UBIAD1 (UbiA prenyltransferase domain-containing protein 1) by directly binding to its 3’-UTR region. UBIAD1 overexpression effectively abrogated the promoting effects of miR-4644 mimic on BCa proliferation, migration, and invasion. Additionally, intratumoral injection of miR-4644 antagomir downregulated miR-4644 expression in tumors and suppressed tumorigenesis in mouse xenografts. Collectively, miR-4644 promotes BCa progression by targeting UBIAD1. miR-4644 may be an important therapeutic target for BCa treatment.