Abstract
Background: RNA-binding motif protein 24 (RBM24) acts as a multifunctional determinant of cell fate, proliferation, apoptosis, and differentiation during development through regulation of pre-mRNA splicing and mRNA stability. It is also implicated in carcinogenesis, but the functions of RBM24 in bladder cancer (BC) remains unclear.Methods: Cell viability was examined by colony forming and MTT assays. Real-time quantitative PCR (RT-qPCR) and western blot analysis were used to detect the protein and mRNA levels. Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) were used to determine the protein-protein interaction. Chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), and oligo pull-down assays were used to verify DNA/RNA–protein interactions. Luciferase assay analysis was used to detect effects on transcription factor activity.Results: In the present study, we revealed that RBM24 was upregulated in BC tissues. Importantly, we found that higher level of RBM24 was correlated with poor prognosis in BC patients. Overexpression of RBM24 promoted while depletion of RBM24 inhibited BC cell proliferation in vivo and in vitro. Mechanically, RBM24 positively regulated Runx1t1 expression in BC cells by binding to and enhancing Runx1t1 mRNA stability. Runx1t1 in turn promoted RBM24 expression by interacting with TCF4. Furthermore, Runx1t1 in turn promoted RBM24 expression by interacting with the transcription factor TCF4 and depressing transcription of miR-625-5p, which directly targets and normally suppresses RBM24 expression. RBM24-regulated BC cells proliferation was moderated via the Runx1t1/TCF4/miR-625-5p feedback loop.Conclusions: In summary, these results indicate that a RBM24/Runx1t1/TCF4/miR-625-5p positive feedback loop plays a key role in BC oncogenesis. Disruption of this pathway may be a potential therapeutic strategy for BC treatment.
ATG7 Promotes Bladder Cancer Invasion via Autophagy‐Mediated Increased ARHGDIB mRNA Stability
