Loss of YTHDC1 m6A reading function promotes invasiveness in urothelial carcinoma of the bladder

Bladder cancer poses significant clinical challenges due to its high metastatic potential and poor prognosis, especially when it progresses to muscle-invasive stages. Here, we show that the m6A reader YTHDC1 is downregulated in muscle-invasive bladder cancer and is negatively correlated with the expression of epithelial‒mesenchymal transition genes. The functional inhibition or depletion of YTHDC1 increased the migration and invasion of urothelial cells. Integrative analysis of multimodal sequencing datasets provided detailed insights into the molecular mechanisms mediating YTHDC1-dependent phenotypes and identified SMAD6 as a key transcript involved in the invasiveness of urothelial carcinoma of the bladder. Notably, SMAD6 mRNA colocalized less with YTHDC1 in tumoral tissues than in paratumoral tissues, indicating disrupted binding during cancer progression. Our findings establish YTHDC1-dependent m6A reading as a critical epitranscriptomic mechanism regulating bladder cancer invasiveness and provide a paradigm for the epitranscriptomic deregulation of cancer-associated networks. Bladder cancer is a common and potentially deadly disease affecting the urinary system. Researchers have identified a protein called YTHDC1, which reads specific RNA modifications (chemical changes to RNA that affect its function), as being less present in more aggressive cases of bladder cancer. This study investigates how YTHDC1 influences the invasiveness of cancer cells. The research involved analyzing bladder cancer samples and conducting experiments on cell models, using RNA sequencing (a method to study the sequence of RNA) and other techniques to understand YTHDC1’s role in cancer progression. Results indicated that lower levels of YTHDC1 are associated with increased cancer cell invasion and migration. The study concludes that YTHDC1 is crucial in preventing cancer spread by regulating specific genes. Future research could explore YTHDC1 as a potential target for bladder cancer treatment. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.