miR-96 regulates FOXO1‑mediated cell apoptosis in bladder cancer

Guo,Yan; Liu,Huihui; Zhang,Hui; Shang,Chao; Song,Yongsheng

doi:10.3892/ol.2012.775

miR-96 regulates FOXO1‑mediated cell apoptosis in bladder cancer

Authors:
- Yan Guo
- Huihui Liu
- Hui Zhang
- Chao Shang
- Yongsheng Song
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Affiliations: Central Laboratory, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China, Department of Basic Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China , Department of Urinary Surgery, The Affiliated Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, P.R. China , Department of Neurobiology, China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: June 27, 2012 https://doi.org/10.3892/ol.2012.775
Pages: 561-565

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Abstract

Transitional cell carcinoma (TCC) is one of the most common types of malignancies and a leading cause of genitourinary system cancer mortality worldwide. The tumor suppressor gene FOXO1, a member of the forkhead box O (FOXO) subfamily of transcription factors, is downregulated in a number of cancers, including TCC; however, the underlying mechanisms are poorly understood. In the present study, we used microRNA (miRNA) target prediction algorithms to identify a conserved potential miR‑96 binding site in the 3'-untranslated region (3'‑UTR) of FOXO1. Using quantitative real‑time PCR (qRT‑PCR) and northern blot analysis, we identified that miR‑96 was downregulated in TCC tissues compared to normal bladder tissues (NB), suggesting that the loss of FOXO1 expression in TCC may be mediated by miR‑96. To confirm this, we transfected pre‑miR‑96/anti‑miR‑96 into the T24 TCC cell line and revealed that miR‑96 expression was sufficient to significantly reduce FOXO1 expression. Conversely, FOXO1 expression was not completely restored by the inhibition of miR‑96 in T24 cells. Moreover, RNA silencing of FOXO1 significantly reduced miR‑96 inhibitor‑mediated T24 cell apoptosis. In conclusion, our study demonstrates that the miR‑96 targeting of FOXO1 is upregulated in TCC; in addition, TCC tumorigenesis may be partly due to the ability of miR-96 to promote FOXO1 repression, thereby bypassing cell apoptosis controls.

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