Abstract
RNA–binding motif protein 24 (RBM24) acts as a multifunctional determinant of cell fate, proliferation, apoptosis, and differentiation during development by regulating premRNA splicing and mRNA stability. It is also implicated in carcinogenesis, but the functions of RBM24 in bladder cancer (BC) remain unclear. In the present study, we revealed that RBM24 was upregulated in BC tissues. Importantly, we found that a higher level of RBM24 was correlated with poor prognosis in BC patients. Overexpression of RBM24 promoted BC cell proliferation, while depletion of RBM24 inhibited BC cell proliferation in vivo and in vitro. Mechanistically, RBM24 positively regulated Runx1t1 expression in BC cells by binding to and enhancing Runx1t1 mRNA stability. Furthermore, Runx1t1 in turn promoted RBM24 expression by interacting with the transcription factor TCF4 and suppressing the transcription of miR-625-5p, which directly targets RBM24 and suppresses RBM24 expression. RBM24-regulated BC cell proliferation was moderated via the Runx1t1/TCF4/miR-625-5p feedback loop. These results indicate that the RBM24/Runx1t1/TCF4/miR-625-5p positive feedback loop participates in BC progression. Disruption of this pathway may be a potential therapeutic strategy for BC treatment.
Highlights
Bladder cancer (BC) is one of the most common malignancies in the urinary system, with an estimated 450,000 new cases per year worldwide[1]
Our results indicate that RNA–binding motif protein 24 (RBM24), Runx1t1, Transcription factor 4 (TCF4), and miR-625-5p form a positive feedback loop that can drive the proliferation of BC cells
Similar results were obtained by immunofluorescence staining with an RBM24-specific antibody in a cohort of 161 BC specimens (Fig. 1c, d), and correlation analysis showed that the level of RBM24 was significantly associated with tumor size and stage but not with other clinicopathologic factors, such as age, sex, or tumor grade (Table 2)
Summary
Bladder cancer (BC) is one of the most common malignancies in the urinary system, with an estimated 450,000 new cases per year worldwide[1]. Among these cases, approximately 70% of new cases are nonmuscleinvasive BC (NMIBC), while 30% are muscle-invasive BC (MIBC)[2]. Chemotherapy, and radiation therapy are the main treatments for BC patients[3]. The 5-year survival rate of high-risk patients is still very low, and the current main treatment methods cannot prevent the recurrence or progression of these BC patients[4]. One important reason is the poor understanding of the mechanisms underlying BC development and progression. It is necessary to better understand the molecular basis of BC and explore innovative therapeutic strategies
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