RBM24 exacerbates bladder cancer progression by forming a Runx1t1/TCF4/miR-625-5p feedback loop
| العنوان: | RBM24 exacerbates bladder cancer progression by forming a Runx1t1/TCF4/miR-625-5p feedback loop |
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| المؤلفون: | Jin-Chun Qi, Bao-Sai Lu, Kai-Long Liu, Ping-Ying Guo, Wei Li, Yue-Wei Yin, Ya-Lin Niu, Zhan Yang, Chen-Ming Zhao |
| المصدر: | Experimental & Molecular Medicine |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, RNA Stability, Clinical Biochemistry, Cell fate determination, medicine.disease_cause, Models, Biological, Biochemistry, Article, Cell growth, Mice, RUNX1 Translocation Partner 1 Protein, Transcription Factor 4, Downregulation and upregulation, Cell Line, Tumor, Biomarkers, Tumor, medicine, Animals, Humans, Gene Regulatory Networks, Molecular Biology, Transcription factor, Aged, Cell Proliferation, Neoplasm Staging, Prostate cancer, Chemistry, RUNX1T1, RNA-Binding Proteins, TCF4, Middle Aged, Prognosis, Gene Expression Regulation, Neoplastic, Disease Models, Animal, MicroRNAs, Urinary Bladder Neoplasms, Apoptosis, Cancer research, Molecular Medicine, Female, RNA Interference, Neoplasm Grading, Carcinogenesis |
| الوصف: | 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. Bladder cancer: Tracking down the molecular mechanisms A protein called RBM24 promotes progression of bladder cancer (BC) by forming a positive feedback loop with a specific transcription factor, driving cancer cell proliferation. Survival rates for BC are low, and the current imperfect understanding of the underlying mechanisms makes it difficult to treat. Ping-Ying Guo at Hebei Medical University in Shijiazhuang, China, and co-workers investigated the role of RBM24, known to be involved in other cancers, and found increased levels in BC tissues. Higher levels were associated with a poor prognosis. Further investigation revealed that RBM24 boosts levels of the transcription factor, which suppresses a molecule that in turn suppresses RBM24, forming a positive feedback loop promoting BC cell proliferation. Interrupting the feedback loop decreased tumor size in a mouse model. These results may help identify better treatments for BC. |
| تدمد: | 2092-6413 1226-3613 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::99b4fa913b693808f5a595abc8b1e6b0Test https://doi.org/10.1038/s12276-021-00623-wTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....99b4fa913b693808f5a595abc8b1e6b0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20926413 12263613 |
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