Comprehensive analysis of aberrantly expressed lncRNAs and construction of ceRNA network in gastric cancer.

Kanagaraj Arun,Servarayan Murugesan Chandramohan,Duraisamy Bennet,Arasambattu Kannan Munirajan,Ganesan Arunkumar,Avaniyapuram Kannan Murugan

doi:10.18632/oncotarget.24841

Abstract

Gastric cancer remains fifth most common cancer often diagnosed at an advanced stage and is the second leading cause of cancer-related death worldwide. Long non-coding RNAs (lncRNAs) involved in various cellular pathways are essential for tumor occurrence and progression and they have high potential to promote or suppress the expression of many genes. In this study, we profiled 19 selected cancer-associated lncRNAs in thirty gastric adenocarcinomas and matching normal tissues by qRT-PCR. Our results showed that most of the lncRNAs were significantly upregulated (12/19). Further, we performed bioinformatic screening of miRNAs that share common miRNA response elements (MREs) with lncRNAs and their downstream mRNA targets. The prediction identified three microRNAs (miR-21, miR-145 and miR-148a) and five gastric cancer-specific target genes (EGFR, KLF4, DNMT1 and AGO4) which also showed strong correlation with lncRNAs in regression analysis. Finally, we constructed an integrated lncRNA-miRNA-mRNA interaction network of the candidate genes to understand the post-transcriptional gene regulation. The ceRNA network analysis revealed that the differentially regulated miR-21 and miR-148a were playing as central candidates coordinating sponging activity of the lncRNAs analyzed (H19, TUG1 and MALAT1) in this study and the overexpression of H19 and miR-21 could be a signature event of gastric tumorigenesis that could serve as prognostic indicators and therapeutic targets.

Highlights

Gastric cancer is the fifth most common cancer and remains as one of the serious global health issues
The competitive endogenous RNA (ceRNA) network analysis revealed that the differentially regulated miR-21 and miR-148a were playing as central candidates coordinating sponging activity of the Long noncoding RNAs (lncRNAs) analyzed (H19, TUG1 and MALAT1) in this study and the overexpression of H19 and miR-21 could be a signature event of gastric tumorigenesis that could serve as prognostic indicators and therapeutic targets
This study is an attempt to delineate the ceRNA mediated molecular mechanism operating in the gastric tumorigenesis at the transcriptional level by analyzing the regulatory interaction between non-coding and proteincoding RNAs

Summary

Introduction

Gastric cancer is the fifth most common cancer and remains as one of the serious global health issues. As per the GLOBOCAN 2012 update, gastric cancer constitutes 6.8% of the total cancer incidences worldwide. The incidence of gastric cancer varies geographically and nearly half of the global incidence is observed in Asia especially in China, Japan, South Korea and Taiwan [1]. More than 95% cases are gastric adenocarcinoma arises at glandular epithelium of stomach due to a wide spectrum of etiological traits like ageing, Helicobacter pylori infection, tobacco chewing, consumption of alcohol, the habit of eating cured meat and salted food [2]. Advances in nextgeneration sequencing and whole transcriptome analysis revealed a wide array of coding and non-coding genes that are frequently involved in gastric cancer and are often linked with different clinical stages and pathological grades [3]

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