Kuo-Wang Tsai1,2,3, Wei-Ting Kuo4,5,6, Shaw-Yeu Jeng7,5. 1. Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C. kwtsai6733@gmail.com kwtsai@ksvgh.gov.tw syjeng@vghks.gov.tw. 2. Department of Chemical Biology, National Pingtung University of Education, Pingtung, Taiwan, R.O.C. 3. Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, R.O.C. 4. Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C. 5. Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C. 6. School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C. 7. Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C. kwtsai6733@gmail.com kwtsai@ksvgh.gov.tw syjeng@vghks.gov.tw.
Abstract
BACKGROUND/AIM: Bladder cancer is the most common malignancy involving the urinary system. The mortality rate in late stages remains high, thus the development of effective biomarkers for diagnosis or prognosis is required in order to improve patient survival rates. Tight junction protein 1 (TJP1) is a membrane-associated protein that helps modulate cell-cell contact. However, the role of TJP1 in bladder cancer progression remains unclear. MATERIALS AND METHODS: The expression levels of TJP1 and miR-455-5p were examined by analyzing The Cancer Genome Atlas database. The biological role of TJP1 and miR-455-5p were assessed in T24 cells with siTJP1 or miR-455-5p mimics transfection, respectively. RESULTS: High levels of expression of TJP1 were significantly correlated with poor lymph node metastasis (pN stage; p=0.004). Knockdown of the TJP1 gene expression led to significant decrease of the growth and invasion of T24 cells. Using a bioinformatics approach, miR-455-5p was shown to suppress TJP1 expression by directly targeting its 3' prime untranslated region in bladder cancer cells. The ectopic expression of miR-455-5p revealed that bladder cancer cell migration, invasion, and proliferation were significantly suppressed. CONCLUSION: In summary, our results indicate that dysfunction of the miR-455-TJP1 axis is involved in bladder cancer cell growth and metastasis. These findings highlight potential therapeutic targets or putative biomarkers for bladder cancer. Copyright
BACKGROUND/AIM: Bladder cancer is the most common malignancy involving the urinary system. The mortality rate in late stages remains high, thus the development of effective biomarkers for diagnosis or prognosis is required in order to improve patient survival rates. Tight junction protein 1 (TJP1) is a membrane-associated protein that helps modulate cell-cell contact. However, the role of TJP1 in bladder cancer progression remains unclear. MATERIALS AND METHODS: The expression levels of TJP1 and miR-455-5p were examined by analyzing The Cancer Genome Atlas database. The biological role of TJP1 and miR-455-5p were assessed in T24 cells with siTJP1 or miR-455-5p mimics transfection, respectively. RESULTS: High levels of expression of TJP1 were significantly correlated with poor lymph node metastasis (pN stage; p=0.004). Knockdown of the TJP1 gene expression led to significant decrease of the growth and invasion of T24 cells. Using a bioinformatics approach, miR-455-5p was shown to suppress TJP1 expression by directly targeting its 3' prime untranslated region in bladder cancer cells. The ectopic expression of miR-455-5p revealed that bladder cancer cell migration, invasion, and proliferation were significantly suppressed. CONCLUSION: In summary, our results indicate that dysfunction of the miR-455-TJP1 axis is involved in bladder cancer cell growth and metastasis. These findings highlight potential therapeutic targets or putative biomarkers for bladder cancer. Copyright