Characterization of long non-coding RNAs and MEF2C-AS1 identified as a novel biomarker in diffuse gastric cancer

Previous studies proved that long noncoding RNAs (lncRNAs) play important role in human cancer. However, the knowledge of genome scale expression of lncRNAs and their potential biological function in gastric cancer is still lacking. Next generation RNA sequencing (RNA-seq) was performed on tumor tissues and matched adjacent normal tissues of six diffuse gastric cancer (DGC) patients. Then we performed a comprehensive analysis on lncRNAs and mRNA. Fifty-eight lncRNAs were upregulated and 54 lncRNAs were downregulated in diffuse gastric cancer tissue compared with adjacent tissue. The numbers of up- and downregulated mRNAs were 306 and 161, respectively. In addition, we inferred the function of lncRNAs by construction of a co-expression network for deregulated mRNAs and lncRNAs. Co-expressed genes of MEF2C-AS1 and FENDRR were enriched to RAS and TGF-beta signaling pathway. MEF2C-AS1 and FENDRR expression were re-evaluated by Real-time Quantitative PCR in 42 DGC patients' tumor and normal tissues, and other 46 DGC patents' and 21 healthy controls' plasma. Validation data showed MEF2C-AS1 and FENDRR were significantly downregulated in tumor tissues compared with normal tissues. And decreased FENDRR are associated with aggressive tumor characteristics including more advanced stage (P = .030), poor differentiation (P = .043) and lymphatic metastasis (P = .001). The expression level MEF2C-AS1 was significantly lower in DGC patients' plasma than that in healthy controls' plasma. In gastric cancer cell lines, knock-down of MEF2C-AS1 or FENDRR reduced the protein levels of FAT3, NTN1 and LYVE1 (the co-expressed genes), which were related with gastric cancer cell proliferation and invasion by previous studies. In addition, knock-down of MEF2C-AS1 or FENDRR promoted aggressive tumor behaviors in in-vitro assays. In this study, we provide a valuable resource of lncRNAs which might play important roles in the function of oncogenes or tumor suppressors affecting the development and progression of diffuse gastric cancer.