• the role of non-coding RNAs (LncRNA) in bladder cancer
  • Mohaddese Gafourifard,1 faezeh Hemmati,2 Sepideh Asadi,3 Neda Sharifi,4 Zahra Babaei,5 Maghsood Mehri,6,*
    1. BSc student of Medical Laboratory Sciences, Student Research Committee, Sarab Faculty of Medical Sciences, Sarab, Iran
    2. BSc student of Medical Laboratory Sciences, Student Research Committee, Sarab Faculty of Medical Sciences, Sarab, Iran.
    3. BSc student of Medical Laboratory Sciences, Student Research Committee, Sarab Faculty of Medical Sciences, Sarab, Iran.
    4. BSc student of Medical Laboratory Sciences, Student Research Committee, Sarab Faculty of Medical Sciences, Sarab, Iran.
    5. BSc student of Medical Laboratory Sciences, Student Research Committee, Sarab Faculty of Medical Sciences, Sarab, Iran.
    6. Department of Medical Genetics, Tabriz University of Medical Sciences, Tabriz, Iran.


  • Introduction: Bladder cancer (BC) is one of the ten most common malignancies worldwide. Apoptosis, glycolysis and EMT are tightly regulated by long non-coding RNAs (lncRNAs) in the BC. LncRNAs are a group of RNA transcripts that do not encode proteins and are over 200 nucleotides in length. They play important roles in controlling cellular pathways and molecular interactions involved in the onset, development, and progression of various types of cancer. The response of BC cells to cisplatin, doxorubicin and gemcitabine chemotherapy is modulated by lncRNAs. LncRNAs regulate immune cell infiltration into the tumor microenvironment and affect BC cell response to immunotherapy. lncRNAs are able to regulate the pathways of microRNA, STAT3, Wnt, PTEN and PI3K/Akt and thus influence both proliferation and migration of BC cells. LncRNAs are potential biomarkers. Defective expression of lncRNAs in tumor cells is a hallmark of cancer, and lncRNAs can act as tumor suppressors or oncogenes depending on the cellular context and different functions of the target genes. This review investigates the role of LncRNA in bladder cancer.
  • Methods: For the subsequent systematic review, the necessary data were collected using the keywords and MeSH (medical title) terms listed below, where possible, and by reference to leading databases such as PubMed and Science Direct. Additionally, a manual search was performed using Google Scholar to increase the sensitivity of the search. The statistical study population includes all studies conducted in context between January 2018 and august 2023. After reviewing relevant results and evidence quality ratings, 12 English-language articles were reviewed.
  • Results: There are more than 100 dysregulated lncRNAs involved in the regulation of various BC biological functions such as cell proliferation, apoptosis and metastasis. 43 Increase in lncRNAs involved in BC proliferation, migration, invasion and cell cycle, such as UCA1, long noncoding RNA 19 (H19), taurine up-regulated gene 1 (TUG1), and Calmodulin Like 3 Antisense RNA 1 (CALML3-AS1). Cytoplasmic lncRNAs can work as oncogenes. UCA1, that overexpressed in bladder cancer, specifically induces Glutaminase 2 (GLS2) by sponging miR-16 and also can activate AKT by recruiting the E1A-binding protein P300 (EP300), which causes bladder cancer cells to grow. UCA1 can has another oncogenic function in bladder cancer by enhancing the mTOR/STAT3/HK2 signaling pathway that promotes the Warburg effect. and UCA1 is also modulated by upstream molecules such as bone morphogenetic protein 9 (BMP9), which then promotes the development of bladder cancer. lncRNA can be found in human biological fluids such as blood and urine. These lncRNAs are resistant to RNases, making them attractive as new non-invasive diagnostic and prognostic biomarkers. It is possible that urine is a better source of biomarkers for genitourinary diseases, including tumors. Common methods for analyzing the expression profile of lncRNAs are real-time polymerase chain reaction (real-time PCR), microarrays and next-generation sequencing (NGS).
  • Conclusion: vital functions of lncRNAs in BC, including: 1) growth regulation, cell cycle, glycolysis and apoptosis factors; 2) regulation of BC cell migration by influencing the EMT mechanism; 3) affect the treatment response and modulate the cytotoxicity of CP, DOX and gemcitabine towards BC cells, 4) regulate the immunosuppressive role of the TME and influence immune cell infiltration; 5) regulation of molecular pathways; and finally 6) considered diagnostic and prognostic. Since BC patients have a poor survival rate, the targeted use of lncRNAs can be considered an important tool to improve their prognosis Circulating lncRNAs can be enriched in urine supernatant and bladder cancer plasma, which could be useful in new bladder cancer tests. The aberrant expression of 36 lncRNAs has been suggested to be closely related to many clinical features of bladder cancer. Given the low and evolutionarily less conserved expression, increased lncRNAs represent advantageous features that may serve as diagnostic or prognostic markers for BC.
  • Keywords: long non-coding RNA, LncRNA, urinary bladder neoplasms, bladder cancer, neoplasms therapeutics