• The role of non-coding RNAs in stemness of bladder cancer cells
  • Morvarid Ghanei,1 Faramarz Khosravi,2,*
    1. Department of Cellular and Molecular Biology, Faculty of Advanced Sciences and technology of Islamic Azad University, Tehran Medical Branch, Tehran, Iran
    2. Tehran Medical sciences,Islamic Azad University,Tehran,Iran.


  • Introduction: In 2025, more than 84,000 new cases of bladder cancer were diagnosed in the United States, and more than 17,000 people died from it. Among the types of cancer cells, cancer stem cells are a type of precursor cell found in most types of cancer. Although these cells make up a tiny percentage (1% to 3%) of all cells in a tumor, it is essential to recognize and find ways to control them because they have the ability to regenerate malignant cells and promote cancer growth. Researchers believe that current cancer treatments sometimes fail because of our inability to completely eliminate cancer stem cells. Identifying and understanding the function of non-coding RNAs as factors in the emergence of cancer stem cells could pave the way for bladder cancer treatment and reduce mortality rates.
  • Methods: In this study, keywords including bladder cancer, non-coding RNA, stem cells and stemness were searched in three databases: Google Scholar, PubMed, and Civilica. Then, screening was performed and studies including other cancers and coding RNAs were excluded.
  • Results: Among the long non-coding RNAs known in bladder cancer is HOXA-AS2. The role of this oncogene was proven in other cancers, including breast cancer, but its effect in bladder cancer was identified in 2019. Inhibition of this RNA in 5637 and T24 bladder cancer cells significantly reduced cancer cell invasion and migration, indicating the ability of HOXA-AS2 to promote bladder cancer cell stemness. SOX2OT is another lncRNA involved in cancer development and cancer stem cells. To prove the effect of this biomarker, comprehensive transcriptome analysis, Western blot, RNA FISH and dual-luciferase reporter assays were performed, and SOX2OT inhibition delayed xenograft tumor growth and reduced metastases in vivo. SNHG1 is one other of long non-coding RNAs that is highly expressed in 95% of muscle-invasive bladder cancers, promoting stem-cell-like sphere formation and enhancing the invasion of cultured bladder cancer cells through the upregulation of Rho GTPase, Rac1. Furthermore, within the circular RNAs, CircRNA_103809 has been recognized in bladder cancer stem cells and functions as a miR-511 sponge, boosting the self-renewal, migration, and invasion abilities of bladder cancer.
  • Conclusion: Focusing on non-coding RNAs could lead to new advances in successful treatment and increased survival for bladder cancer patients. Inhibiting these RNAs limits the stemness of cancer cells and helps to increase the effectiveness of interventions.
  • Keywords: Bladder cancer, cancer stem cells, non-coding RNA