MiR-421 regulates apoptosis of BGC-823 gastric cancer cells by targeting caspase-3.

Jian-Hong Wu,Jian-Jun Wang,Ze-You Wang,Yi-Biao Jiang,Tao Gu,Xian Zhang,Yong-Liang Yao,Xiong-Yong Pu,Wang-Wei Sun

doi:10.7314/apjcp.2014.15.13.5463

Abstract

MicroRNAs might act as oncogenes or tumor suppressors in cancer. Recent studies have shown that miR-421 is up-regulated in human gastric cancer. Here, we found that miR-421 was over-expressed in gastric cancer tissues and cell lines. Bioinformatics analysis predicted that the caspase-3 gene was a target of miR-421. Caspase-3 was negatively regulated by miR-421 at the post-transcriptional level. Bax and Bcl-2 were also regulated by miR-421. Moreover, tumor necrosis factor receptor-I and -II, death receptors in the apoptosis pathway, were up-regulated by miR-421. The over-expression of miR-421 promoted gastric cancer cell growth and inhibited apoptosis of the BGC-823 gastric cancer cell line. These observations indicate that miR-421 acts as a tumor promoter by targeting the caspase-3 gene and preventing apoptosis of gastric cancer cells through inhibition of caspase-3 expression. These findings contribute to our understanding of the functions of miR-421 in gastric cancer.

Highlights

Gastric cancer is one of the major malignant diseases,which is the second most common and the leading cause of cancer mortality around world, with about 1,000,000 new cases every year (Yang 2006)
It is estimated that 50% of gastric cancer cases especially in Asia, where China, Japan and Korea have the highest incidence in the world (Ferlay et al, 2010). (Saeki et al, 2013) revealed prostate stem cell antigen (PSCA) gene and Mucin 1 (MUC1) gene were related to human gastric cancer, certain strains of H. pylori assisted by some of its virulence factors play a critical role in gastric cancer development, which influence cellular proliferation signaling, the expression of cell proliferation regulating genes or the progression of gastric cancer (Kim et al, 2011), but successful therapeutic targets are limited
MiR‐421 expression in gastric cancer cells To investigate the role of miR-421 in gastric cancer cells, the expression levels of miR-421 were first measured in 50 cases of human gastric cancer tissues, pericarcinoma tissues, and normal gastric tissues by quantitative PCR (Figure 1A)

Summary

Introduction

Gastric cancer is one of the major malignant diseases,which is the second most common and the leading cause of cancer mortality around world, with about 1,000,000 new cases every year (Yang 2006). MicroRNAs (miRNAs) are small regulatory noncoding RNAs that bind to specific target mRNAs, leading to translational repression. MiRNAs act as negative regulators of gene expression, which are involved in the regulation of biological processes including cell growth, differentiation, and apoptosis in both physiological conditions and disease states such as tumors (He et al, 2004; Bartel 2009). Ataxia-telangiectasia mutated (ATM) is a high molecular weight protein serine/threonine kinase, which plays a important role in the maintenance of genomic integrity by activating checkpoints of cell cycles or promoting the repair of DNA double-strand breaks. Multi-target anti-microRNA antisense oligonucleotide (MTg-AMOs) can inhibit the expression of multiple miRNAs, and effectively antagonize proliferation and migration of gastric cancer cells promoted by oncomirs (Xu et al, 2012)

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