Journal
ONCOLOGY LETTERS
Volume 4, Issue 3, Pages 561-565Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2012.775
Keywords
bladder transitional cell carcinoma; miR-96; forkhead box protein O1; apoptosis
Categories
Funding
- National Nature Science Foundation of China [81172577]
- Education Science and Technology Research Project of Liaoning Province, China [L2011130]
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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 ICC; in addition, ICC tumorigenesis may be partly due to the ability of miR-96 to promote FOXO1 repression, thereby bypassing cell apoptosis controls.
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