Transcription Factors and microRNA-Co-Regulated Genes in Gastric Cancer Invasion in Ex Vivo

Yue Shi,Fan Li,Jihan Wang,Zipeng Duan,Guoqing Wang,Zhuoyuan Xin,Jian-Jun Zhao

doi:10.1371/journal.pone.0122882

Abstract

Aberrant miRNA expression abnormally modulates gene expression in cells and can contribute to tumorigenesis in humans. This study identified functionally relevant differentially expressed genes using the transcription factors and miRNA-co-regulated network analysis for gastric cancer. The TF-miRNA co-regulatory network was constructed based on data obtained from cDNA microarray and miRNA expression profiling of gastric cancer tissues. The network along with their co-regulated genes was analyzed using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Transcriptional Regulatory Element Database (TRED). We found eighteen (17 up-regulated and 1 down-regulated) differentially expressed genes that were co-regulated by transcription factors and miRNAs. KEGG pathway analysis revealed that these genes were part of the extracellular matrix-receptor interaction and focal adhesion signaling pathways. In addition, qRT- PCR and Western blot data showed an increase in COL1A1 and decrease in NCAM1 mRNA and protein levels in gastric cancer tissues. Thus, these data provided the first evidence to illustrate that altered gene network was associated with gastric cancer invasion. Further study with a large sample size and more functional experiments is needed to confirm these data and contribute to diagnostic and treatment strategies for gastric cancer.

Highlights

Gastric cancer is one of the most common form of malignancies in the world, contributing to a third of cancer-related deaths in men and a fifth among women [1]
Data from the cDNA and miRNA microarray was used to construct the transcription factors-miRNA co-regulatory network in gastric cancer and identified 18 hubgenes that were regulated by both transcription factors and miRNAs
Transcription factors MYB, MYBL2, ETV4, LEF1,TFAP2A were up-regulated in gastric cancer tissues

Summary

Introduction

Gastric cancer is one of the most common form of malignancies in the world, contributing to a third of cancer-related deaths in men and a fifth among women [1]. Two-thirds of gastric cancer cases occur in the developing countries. In China, the incidence and mortality related to gastric cancer ranks third among other forms of malignancies [2] and it was reported that gastric cancer occurs more frequently in rural areas and with a trend of younger people being affected by it in recent years [3]. Environmental (such as Helicobacter pylori infection or consumption of smoked foods) and genetic factors (E-cadherin mutation) increases the susceptibility to gastric cancer by inducing alterations in oncogenes/tumor suppressor genes and/or.

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Conclusion