MiR-34a inhibits proliferation and invasion of bladder cancer cells by targeting orphan nuclear receptor HNF4G.

Huaibin Sun,Jun Tian,Tingting Xie,Wanhua Xian,Xiangdong Yang

doi:10.1155/2015/879254

Huaibin Sun, Jun Tian + Show 3 more

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https://doi.org/10.1155/2015/879254

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Journal: Disease markers	Publication Date: Jan 1, 2015
Citations: 58	License type: CC BY 3.0

Affiliation: Qilu Hospital of Shandong University

Abstract

miR-34a is a member of the miR-34 family and acts as a tumor suppressor in bladder cancer. This study explored the regulative role of miR-34a on an orphan nuclear receptor HNF4G, which has a well-confirmed role in bladder tumor growth and invasion. qRT-PCR analysis was applied to measure miR-34a expression in two tumorigenic bladder cancer cell lines 5637 and T24 and one normal human urothelial cell line SV-HUC-1. Luciferase assay was performed to verify the putative binding between miR-34a and HNF4G. The influence of miR-34a-HNF4G axis on cell viability, colony formation, and invasion was assessed with loss- and gain-of-function analysis. This study observed that the miR-34a expressions in 5637 and T24 cells were significantly lower than in SV-HUC-1, while the muscle invasive cell sublines 5637-M and T24-M had even lower miR-34a expression than in the nonmuscle invasive sublines. HNF4G has a 3′-UTR binding site with miR-34a and is a direct downstream target of miR-34a. miR-34a can directly downregulate the expression of HNF4G and thus inhibit tumor cell viability, colony formation, and invasion. Therefore, miR-34a-HNF4G axis is an important pathway modulating cell viability, proliferation, and invasion of bladder cancer cells.

Highlights

Bladder cancer is a common urinary malignant tumor characterized as high recurrence rate
MicroRNAs are a group a conservative, small (19–25 nucleotides in length), and noncoding RNAs repressing translation or promoting degradation of target mRNA through binding to the complementary sequences in the 3󸀠 untranslated region (3󸀠-UTR) [4]. miRNAs can be either tumor suppressors or oncogenes depending on their target genes in different cancers [5, 6]
We explored the regulative network of miR-34a in bladder cancer and firstly reported that HNF4G is a direct downstream target of miR-34a. miR-34a could suppress tumor cell proliferation and invasion through suppressing HNF4G expression

Summary

Introduction

Bladder cancer is a common urinary malignant tumor characterized as high recurrence rate. MiRNAs can be either tumor suppressors or oncogenes depending on their target genes in different cancers [5, 6]. MiR-34a is the most significantly regulated downstream miRNA of the p53 pathway and its expression influences cell apoptosis, cell-cycle arrest, senescence, and cancer cell chemosensitivity [10,11,12,13]. One recent study observed that orphan NR HNF4G was remarkably upregulated in bladder cancer and this upregulation gives rise to bladder cancer progression through promoting cancer cell growth and invasion [16]. We explored the regulative network of miR-34a in bladder cancer and firstly reported that HNF4G is a direct downstream target of miR-34a. MiR-34a could suppress tumor cell proliferation and invasion through suppressing HNF4G expression We explored the regulative network of miR-34a in bladder cancer and firstly reported that HNF4G is a direct downstream target of miR-34a. miR-34a could suppress tumor cell proliferation and invasion through suppressing HNF4G expression

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