Tài liệu Báo cáo khoa học: MicroRNA-23a promotes the growth of gastric adenocarcinoma cell line

MicroRNA-23a promotes the growth of gastric

adenocarcinoma cell line MGC803 and downregulates

interleukin-6 receptor

Li-Hua Zhu1,2,*, Tao Liu1,*, Hua Tang1

, Rui-Qing Tian1

, Chang Su1

, Min Liu1 and Xin Li1

1 Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin, China

2 Department of Pathobiology, Bioscience Faculty, North China Coal Medical College, Tangshan, China

Introduction

Recent findings have shown that, as regulation factors

of gene expression, microRNAs (miRNAs) are often

overexpressed or downregulated in a number of human

malignancies, and some can also function as tumor

suppressors or oncogenes [1]. miRNA genes are fre￾quently located in cancer-associated genomic regions

or in fragile sites [2]. Previous studies have identified

cancer-specific miRNAs in many types of cancer,

including B-cell chronic lymphoblastic leukemia [3],

lung cancer [4], colorectal cancer [5,6], breast cancer

[7], papillary thyroid cancer [8] and hepatocellular

carcinoma [9]. Gastric cancer is the second most

common cause of cancer deaths worldwide. Previous

studies have revealed several genes related to human

gastric cancer [10,11], but the common molecular mech￾anisms of gastric cancer remain to be elucidated. Gastric

cancer is a complex genetic disease, in which the expres￾sion of many specific genes, known as oncogenes or

tumor suppressors, is abnormally altered. It has been

reported that microRNA-34 (miR-34) is involved in the

p53-directed tumor suppressor network in gastric cancer

[12]. Our previous study showed that miR-27a functions

as an oncogene in gastric adenocarcinoma by targeting

prohibitin [13]. In the current study, we examine the

differential expression of miR-23a in gastric cancer and

normal gastric tissues, and identify that miR-23a can

Keywords

cell growth; gastric adenocarcinoma; IL6R;

miR-23a; target gene

Correspondence

H. Tang, Tianjin Life Science Research

Center and Basic Medical School, Tianjin

Medical University, Tianjin 300070, China

Fax: +86 22 23542503

Tel: +86 22 23542503

E-mail: [email protected]

*These authors contributed equally to this

work

(Received 11 April 2010, revised 15 June

2010, accepted 12 July 2010)

doi:10.1111/j.1742-4658.2010.07773.x

MicroRNAs are an evolutionarily conserved class of endogenous noncod￾ing RNAs that modulate gene expression at the post-transcriptional level.

Recently, microRNA-23a (miR-23a) has been found to function as a

growth-promoting and antiapoptotic factor in hepatocellular carcinoma

cells. Our previous study showed that miR-23a was significantly upregulat￾ed in gastric adenocarcinoma tissues. In this study, we found that miR-23a

promoted the proliferative potential of gastric adenocarcinoma cell line

MGC803. We also identified IL6R as a direct target gene for miR-23a

using a fluorescent reporter assay. The mRNA and protein levels of IL6R

were both inversely correlated with the miR-23a expression level. Our

results demonstrate that miR-23a can target IL6R and promote the growth

activity of gastric adenocarcinoma cells in vitro. The downregulation of

IL6R by miR-23a may explain why the suppression of miR-23a can inhibit

gastric cancer cell proliferation.

Abbreviations

ASO, antisense oligonucleotide; EGFP, enhanced green fluorescence protein; GAPDH, glyceraldehyde phosphate dehydrogenase;

IL6R, interleukin-6 receptor; miR-23a, microRNA-23a; miRNA, microRNA; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide;

siRNA, small interfering RNA; UTR, untranslated region.

3726 FEBS Journal 277 (2010) 3726–3734 ª 2010 The Authors Journal compilation ª 2010 FEBS