miRNA-556-3p promotes human bladder cancer proliferation, migration and invasion by negatively regulating DAB2IP expression

Feng,Chen; Sun,Ping; Hu,Jing; Feng,Hua; Li,Mingqiu; Liu,Guibo; Pan,Yanming; Feng,Ying; Xu,Yongliang; Feng,Kejian; Feng,Yukuan

doi:10.3892/ijo.2017.3969

miRNA-556-3p promotes human bladder cancer proliferation, migration and invasion by negatively regulating DAB2IP expression

Authors:
- Chen Feng
- Ping Sun
- Jing Hu
- Hua Feng
- Mingqiu Li
- Guibo Liu
- Yanming Pan
- Ying Feng
- Yongliang Xu
- Kejian Feng
- Yukuan Feng
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Affiliations: Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang, Heilongjiang, P.R. China, School of Basic Medical Science, Mudanjiang Medical University, Mudanjiang, Heilongjiang, P.R. China, Department of Neurology, The Second Affiliated Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang, P.R. China
Published online on: April 20, 2017 https://doi.org/10.3892/ijo.2017.3969
Pages: 2101-2112

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Abstract

MicroRNAs (miRNAs) play critical roles in tumorigenesis and metastasis by negatively regulating gene expression through complementary binding to the 3'-untranslated region of target mRNAs. The role of miRNAs in expression of the tumor suppressor DAB2IP in bladder cancer (BC) remains unknown. The aim of the present study was to identify miRNAs targeting DAB2IP and determine their expression and function in BC. We predicted candidate miRNAs targeting DAB2IP using TargetScan software. Dual-luciferase reporter assays confirmed that miRNA-556-3p directly regulated DAB2IP expression. Quantitative RT-PCR and RNase protection assays showed that endogenous miRNA-556-3p expression was significantly upregulated in clinical samples of BC patients and BC cell lines and western blot analysis indicated that DAB2IP expression in BC tissues and BC cell lines was concurrently downregulated. Gain or loss of function studies showed that upregulation of miRNA-556-3p promoted proliferation, invasion, migration and colony formation of BC cells, whereas downregulation resulted in opposite effects. Importantly, restoration of DAB2IP expression rescued the effects induced by miRNA-556-3p. Overexpression of miRNA-556-3p in BC cells not only decreased DAB2IP expression, but also markedly increased Ras GTPase activity and ERK1/2 phosphorylation level. These findings suggest that DAB2IP is a direct target of miRNA-556-3p, and endogenous miRNA-556-3p expression shows inverse correlation with simultaneous DAB2IP expression in BC tissues and cells. miRNA-556-3p functions as a tumor promoter in tumorigenesis and metastasis of BC by targeting DAB2IP. Moreover, miRNA-556-3p-mediated DAB2IP suppression plays an oncogenic role by partial activation of the Ras-ERK pathway.

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