Tissue-Specific Down-Regulation of the Long Non-Coding RNAs PCAT18 and LINC01133 in Gastric Cancer Development

Abstract

Gastric cancer (GC) is the fifth most common cancer and the third most frequent cause of cancer deaths worldwide. The high death rate associated with GC, and lack of appropriate biomarkers for diagnosis, prognosis, and treatment emphasize the need for identification of novel molecules. Given the emerging roles for long non-coding RNAs (lncRNAs) in cancer development, we studied novel lncRNA candidates involved in gastric carcinogenesis. LncRNA candidate discovery was performed using analyses of available datasets and literature. Validation was done using an internal sample set of GC/normal tissues, and external independent datasets. Network analysis and functional annotation of co-expressed protein coding genes were performed using the weighted gene correlation network analysis (WGCNA) and ingenuity pathway analysis. Two novel lncRNAs, PCAT18 and LINC01133, associated with GC development were identified by analysis of the discovery Gene Expression Omnibus (GEO) datasets. The down-regulation of these genes in GC tissues was successfully validated internally and externally. The results showed a tissue-specific down-regulation of PCAT18 and LINC01133 in gastrointestinal tissues. WGCNA and ingenuity pathway analyses revealed that the genes co-expressed with the two lncRNAs were mostly involved in metabolic pathways and networks of gastrointestinal disease and function. Our findings of a tissue-specific down-regulation of PCAT18 and LINC01133 in gastric and other gastrointestinal cancers imply that these lncRNAs may have a tumor suppressive function in the development of these tumor entities. The two lncRNA biomarkers may contribute to a better understanding of the complex mechanisms of gastric carcinogenesis.

Keywords

• gastric cancer
• long noncoding RNA
• gene expression
• tumor suppressor
• GEO and TCGA databases