PF171 DIFFERENTIAL EXPRESSION PATTERNS OF SPECIFIC LONG NONCODING RNAS AND COMPETING ENDOGENOUS RNA NETWORK IN ACUTE LYMPHOCYTE LEUKEMIA

Abstract

Background: Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) play an important role in the competitive endogenous RNA (ceRNA) networks in that they regulate protein-coding gene expression by sponging microRNAs (miRNAs). However, the roles of specific lncRNA and its related competing endogenous RNAs (ceRNA) network in acute lymphocyte leukemia (ALL) are not fully understood. Aims: The aims of this study were to use RNA expression profile bioinformatics data from cases of ALL from the Cancer Genome Atlas (TCGA), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the Gene Ontology (GO) databases to construct a ceRNA network of mRNAs, lncRNAs, and miRNAs. Methods: All patient databases were obtained from TCGA database. lncRNA and mRNA expression files included leukemia and corresponding normal samples were also downloaded from TCGA portal. An EdgeR (empirical analysis of digital gene expression data in R) package was used to identify the RNAseq data of acute lymphoblastic leukemia. Only the differential expression genes (DEGs) with adj.P.Val < 0.05 and |log2fold change (FC)| ≥ 2 were considered as significant. Based on bioinformatics generated from miRcode, starBase, and miRTarBase, we constructed an lncRNA-miRNA-mRNA network (ceRNA network) in ALL. Database for annotation, visualization and integrated discovery (DAVID), was used for GO analysis to understand the functions of targeted genes in terms of biological process (BP), cellular component (CC) and molecular function (MF). In addition, KEGG and an R Package, clusterProfiler, was distinguished pathway enrichment of each targeted gene. Cutoff value was set as P value < 0.05. Results: We found 755 differentially expressed lncRNAs and 6131 differentially expressed genes (DEGs). The functional enrichment indicated that the DEGs mainly regulated the pathways of programmed cell death, cell cycle, apoptosis and so on. Through integrated lncRNA-mRNA and miRNA-mRNA pairs, the ceRNA network was constructed. The resulting ceRNA network included 395 mRNAs, 135 lncRNAs and 31 miRNAs. 18 out of the 135 lncRNAs (RP11-497G19.2, LOC339535, LA16c-329F2.1, AK127309, XLOC_006664, RP1-16A9.1, RP11-69I8.3, LOC100507254, KB-1183D5.14, LOC100506305, RP11-87C12.5, WASIR1, RP3-523C21.1, RP11-325F22.2, AC002454.1, LOC286367, LOC286367, RP3-523C21.2) were identified and found to be associated with the complete remission rate of ALL patients (P < 0.05)Summary/Conclusion: Our results showed lncRNA expression patterns and a complex ceRNA network in ALL. Furthermore, we identified 18 lncRNAs as novel, potential prognostic biomarkers for ALL. However, futher studies on verification of ceRNA network are needed.