Abstract: Background: Bladder cancer (BC) is a highly heterogeneous stem cell disease. Cancer stem cells (CSCs) are the drivers of tumor growth and recurrence, with the ability to self-renew, metastasize, and resist chemotherapy. However, the specific molecular mechanisms of CSCs driving BC recurrence and progression remains unclear. Objective: To explore the underlying molecular mechanism of CSCs driving BC recurrence and progression. Methods: Tumor xenograft model in vivo was established after 4-6-week-old male nude mice were subcutaneously injected with 5×106 of T24 and 5637 cells in 0.1 mL 50% Matrigel. Pearson correlation analysis analyzed the correlation between miR-582-5p and CD81, and which was furtherly verified by dual-luciferase reporter gene assay. Sphere formation assay, flow cytometry, immunohistochemistry (IHC), qRT-PCR and Western blot were carried to examine sphere formation, ALDHhigh populations, the level of genes and proteins. Multivariate analysis was carried to explore the factors associated with recurrence free survival of BC patients. Results: MiR-582-5p was down-regulated in patients with BC, and miR-582-5p overexpression negatively correlated with BC stemness. Mechanically, miR-582-5p negatively targeted to CD81. Functionally, miR-582-5p overexpression inhibited BC stemness and recurrence via targeting CD81. Conclusion: Our study illustrated that miR-582-5p inhibited cell stemness and recurrence via targeting CD81 in BC. Our findings illustrated the specific molecular mechanism of miR-582-5p inhibiting BC progression. MiR-582-5p may serve as the novel biomarker for BC clinical therapeutics and prognosis.

Journal Link: 10.21203/rs.3.rs-1625201/v1 Journal Link: Publisher Website Journal Link: Download PDF Journal Link: Google Scholar