MiR-34a regulates apoptosis in liver cells by targeting the KLF4 gene

Qiu Chen,Wei Liu,Lei Li,Feng Cui,Lu Zheng,Jian Cao,Yu Tu,Jun Hou,Shu Zhang,Xue Zuo,Yong He,Wei Zhu

doi:10.2478/s11658-013-0115-y

Abstract

MicroRNAs (miRNAs) regulate gene expression by inhibiting translation or targeting messenger RNA (mRNA) for degradation in a posttranscriptional fashion. In this study, we show that ectopic expression of miR-34a-5p reduces the mRNA and protein levels of Krüppel-like factor 4 (KLF4). We also demonstrate that miR-34a targets the 3′-untranslated mRNA region of KLF4 and show that overexpression of miR-34a induces a significant level of apoptosis in BNL CL.2 cells exposed to doxorubicin or 10 Gy X-ray. Our data suggest that the effects of miR-34a on apoptosis occur due to the downregulation of KLF4.

Highlights

MicroRNA is defined as a small regulatory RNA molecule consisting of non-coding RNA of about 22 nucleotides in length
Krüppel-like factor 4 (KLF4) is one of the target genes for miR-34a-5p in BNL CL.2 cells The miR-34a-KLF4 target prediction was derived from miRanda [21], miRBase [22] and PicTar [23]
KLF4 messenger RNA (mRNA) expression was increased in BNL CL.2 cells after miR-34a-5p inhibitor transfection (Fig. 2B, right panel)

Summary

Introduction

MicroRNA (miRNA) is defined as a small regulatory RNA molecule consisting of non-coding RNA of about 22 nucleotides in length. The current data suggest that exposure to radiation provokes cellular responses controlled in part by gene expression networks [8, 9]. MicroRNAs regulate gene expression and have been shown to control multiple intracellular processes involved in the response to cellular stress [10, 11]. MiR-34a is known to regulate a plethora of target proteins that induce cell apoptosis in a p53-dependent or independent manner [16, 17]. The function of miR-34a in radiation-induced apoptosis, which involves the inhibition of its target genes, is still unclear. We found that miR-34a-5p could be induced in BNL CL. cells by radiation. Over-expression of miR-34a-5p and knockdown of KLF4 could significantly enhance the apoptosis of BNL CL. cells

Methods

Results

Conclusion