Novel oncogenic function of mesoderm development candidate 1 and its regulation by MiR-574-3p in bladder cancer cell lines

Tatarano,Shuichi; Chiyomaru,Takeshi; Kawakami,Kazumori; Enokida,Hideki; Yoshino,Hirofumi; Hidaka,Hideo; Nohata,Nijiro; Yamasaki,Takeshi; Gotanda,Takenari; Tachiwada,Tokushi; Seki,Naohiko; Nakagawa,Masayuki

doi:10.3892/ijo.2011.1294

Novel oncogenic function of mesoderm development candidate 1 and its regulation by MiR-574-3p in bladder cancer cell lines

Authors:
- Shuichi Tatarano
- Takeshi Chiyomaru
- Kazumori Kawakami
- Hideki Enokida
- Hirofumi Yoshino
- Hideo Hidaka
- Nijiro Nohata
- Takeshi Yamasaki
- Takenari Gotanda
- Tokushi Tachiwada
- Naohiko Seki
- Masayuki Nakagawa
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Affiliations: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan, Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
Published online on: December 13, 2011 https://doi.org/10.3892/ijo.2011.1294
Pages: 951-959
Copyright: © Tatarano et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Our previous studies suggested that microRNA (miR)-574-3p is a candidate tumor suppressor microRNA (miRNA) in human bladder cancer (BC). Among 17 down-regulated miRNAs, miR-574-3p is located on chromosome 4p14 where we had identified a chromosomal loss region by array-CGH in BC cell lines. MiR-574-3p expression was down-regulated in BC cell lines. Gain-of-function analysis revealed that cell proliferation, migration and invasion were significantly inhibited in miR‑574‑3p-transfected BC cell lines. Flow cytometry analysis showed that cell apoptosis was induced in miR-574-3p transfectants. Oligo microarray analysis suggested that the mesoderm development candidate 1 (MESDC1) gene was a target gene in miR-574-3p transfectants. Luciferase assays revealed that miR‑574‑3p was directly bound to MESDC1 mRNA. MESDC1 is predicted to be a novel actin-binding protein located on chromosome 15q13. Although the gene is conserved among many species, its functional role is still unknown in both human malignancies and normal tissues. Loss-of-function studies demonstrated that cell proliferation, migration and invasion were significantly inhibited in si-MESDC1-transfected BC cell lines. Flow cytometry analysis showed that apoptosis was induced in si-MESDC1 transfectants. We are the first to demonstrate that miR-574-3p is a miRNA with tumor suppressor function and that MESDC1 (which has a potential oncogenic function in BC) may be targeted by miR-574-3p.

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