Comprehensive analysis of aberrantly expressed lncRNAs and construction of ceRNA network in gastric cancer
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Kanagaraj Arun1,*, Ganesan Arunkumar1,*, Duraisamy Bennet2, Servarayan Murugesan Chandramohan2, Avaniyapuram Kannan Murugan3 and Arasambattu Kannan Munirajan1
1Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600 113, India
2Institute of Surgical Gastroenterology, Rajiv Gandhi Government General Hospital and Madras Medical College, Chennai – 600 001, India
3Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh-11211, Saudi Arabia
*These authors contributed equally to this work
Keywords: gastric cancer; lncRNA; ceRNA; competing endogenous RNA; miRNA
Received: September 13, 2017 Accepted: February 28, 2018 Published: April 06, 2018
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.
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