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34 Innovative drug discovery for bladder cancer: Targeting miR – 130 family molecules using locked nucleic acids
Title
34
Innovative drug discovery for bladder cancer: Targeting miR‑130 family molecules using locked nucleic acids Eur Urol Suppl 2015;14/2;e34
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Uemura M. 1 , Egawa H.2 , Nakata W.1 , Fujita K. 1 , Jingushi K. 2 , Tsujikawa K. 2 , Nonomura N.1 1 Osaka
University Graduate School of Medicine, Dept. of Urology, Suita, Japan, 2 Osaka University Graduate School of Pharmaceutical
Sciences, Laboratory of Molecular and Cellular Physiology, Suita, Japan INTRODUCTION & OBJECTIVES: Bladder cancer is the 9th leading cause of cancer with 430,000 new cases occurring in 2012. Untreated metastatic urothelial carcinoma (UC) is associated with a median survival time rarely exceeding 3 to 6 months. It is a chemotherapysensitive tumor, and cisplatin-based chemotherapy is the standard treatment, without an approved or established option for second-line treatment. Here, to identify a novel biomarker or molecular target in UC therapy, we focused on microRNA (miRNA) expression signatures obtained from UC clinical specimens by microarray analysis. MATERIAL & METHODS: We analyzed the functional significance of miR-130 family molecules in bladder cancer cell lines using LNAs (Locked Nucleic Acids) to suppress miR-130 family expression. The LNAs were designed to inhibit the entire miR-130 family by targeting a common seed sequence.
Fig 1 sequence of miR-130 family Fig 2 miR-130 family-targeted LNA
file:///S|/IM/EURSUP/2015%20EAU%20Abstracts/content/data/34.html[19/02/2015 08:11:26]
Title RESULTS: We found that the miR-130 family (miR-130b, miR-301a and miR-301b) were significantly upregulated in bladder cancer compared to normal specimens. Combinatorial inhibition of all MiR-130 family molecules using our targeted LNAs suppressed cell proliferation, cell migration and cell invasion of bladder cancer cell lines more powerfully than siRNA-mediated inhibition of any single family member. Furthermore, treatment with miR-130 family-targeted LNAs dramatically inhibited tumor growth in a murine xenograft model.
Fig 3 miR-130 family-targeted LNA dramatically inhibits tumor growth in vivo. CONCLUSIONS: The miR-130 family has a crucial role in the malignant progression of bladder cancer, and thus LNA targeting the miR-130 family could become promising drugs in the treatment of bladder cancer.
file:///S|/IM/EURSUP/2015%20EAU%20Abstracts/content/data/34.html[19/02/2015 08:11:26]
34
Innovative drug discovery for bladder cancer: Targeting miR‑130 family molecules using locked nucleic acids Eur Urol Suppl 2015;14/2;e34
Print! Print!
Uemura M. 1 , Egawa H.2 , Nakata W.1 , Fujita K. 1 , Jingushi K. 2 , Tsujikawa K. 2 , Nonomura N.1 1 Osaka
University Graduate School of Medicine, Dept. of Urology, Suita, Japan, 2 Osaka University Graduate School of Pharmaceutical
Sciences, Laboratory of Molecular and Cellular Physiology, Suita, Japan INTRODUCTION & OBJECTIVES: Bladder cancer is the 9th leading cause of cancer with 430,000 new cases occurring in 2012. Untreated metastatic urothelial carcinoma (UC) is associated with a median survival time rarely exceeding 3 to 6 months. It is a chemotherapysensitive tumor, and cisplatin-based chemotherapy is the standard treatment, without an approved or established option for second-line treatment. Here, to identify a novel biomarker or molecular target in UC therapy, we focused on microRNA (miRNA) expression signatures obtained from UC clinical specimens by microarray analysis. MATERIAL & METHODS: We analyzed the functional significance of miR-130 family molecules in bladder cancer cell lines using LNAs (Locked Nucleic Acids) to suppress miR-130 family expression. The LNAs were designed to inhibit the entire miR-130 family by targeting a common seed sequence.
Fig 1 sequence of miR-130 family Fig 2 miR-130 family-targeted LNA
file:///S|/IM/EURSUP/2015%20EAU%20Abstracts/content/data/34.html[19/02/2015 08:11:26]
Title RESULTS: We found that the miR-130 family (miR-130b, miR-301a and miR-301b) were significantly upregulated in bladder cancer compared to normal specimens. Combinatorial inhibition of all MiR-130 family molecules using our targeted LNAs suppressed cell proliferation, cell migration and cell invasion of bladder cancer cell lines more powerfully than siRNA-mediated inhibition of any single family member. Furthermore, treatment with miR-130 family-targeted LNAs dramatically inhibited tumor growth in a murine xenograft model.
Fig 3 miR-130 family-targeted LNA dramatically inhibits tumor growth in vivo. CONCLUSIONS: The miR-130 family has a crucial role in the malignant progression of bladder cancer, and thus LNA targeting the miR-130 family could become promising drugs in the treatment of bladder cancer.
file:///S|/IM/EURSUP/2015%20EAU%20Abstracts/content/data/34.html[19/02/2015 08:11:26]