- Review
The Crossroads of Cancer Regulation: Discussing the Role of Non-Coding RNAs in Bladder Cancer Stem Cells
- Alexandros Georgiou,
- Dimitrios Triantis and
- Maria Goulielmaki
- + 1 author
Despite substantial progress in the field of bladder cancer management, the disease continues to represent an important health issue characterized by increased recurrence and progression rates. This is largely attributed to cancer stem cells (CSCs), a unique cell subpopulation capable of self-renewal, differentiation and resistance to conventional anti-cancer therapies. At the same time, our understanding of cancer biology has been revolutionized by the identification of non-coding RNAs (ncRNAs), a heterogeneous group of RNA molecules that do not translate into proteins yet function as pivotal regulators of gene expression. Emerging evidence demonstrates that ncRNAs modulate key hallmarks of CSCs, including self-renewal, epithelial–mesenchymal transition and drug resistance. This review investigates the intricate interplay between ncRNAs and the core signaling pathways that underlie bladder CSC biology. Unravelling the nexus between CSCs and ncRNAs is crucial for developing novel diagnostic biomarkers, better prognostic tools and innovative therapeutic strategies for patients with bladder cancer.
11 December 2025



![Summary of the provided examples regarding the regulatory role of ncRNAs in BCSCs. The lncRNA XIST acts as a molecular sponge for miR-200c, a tumor-suppressing miRNA that is frequently downregulated in various tumors. Through miR-200c inhibition, XIST promotes stem-like properties and EMT (A) [60]. CircRNA_103809 was found to be upregulated in BCSCs, acting as a molecular sponge for miR-511, another tumor-suppressing miRNA that inhibits sphere formation and reduces the migration and invasive capacities of these cells (B) [61]. Lnc-DILC modulates the IL-6/STAT3 pathway, acting as a negative regulator of BCSCs by inhibiting sphere formation, reducing the CSC population and suppressing the expression of key stemness-associated factors (C) [62]. The lncRNA SNHG1 recruits DNMT3A to the promoter region of miR-129-2-5p, leading to its hypermethylation and silencing. The resulting decrease in miR-129-2-5p levels leads to an amplified Rac1 protein level, increasing the number of formed spheres and promoting the invasive capacity of BCSCs (D) [65]. Created in BioRender. Georgiou, A. (2025) https://BioRender.com/jol1go7.](https://mdpi-res.com/uro/uro-05-00022/article_deploy/html/images/uro-05-00022-g001-550.jpg)

