Identification of novel lncRNAs involved in the pathogenesis of childhood acute lymphoblastic leukemia

Sheng Li; Hongliang Bian; Yizhi Cao; Chenxia Juan; Qian Cao; Guoping Zhou; Yongjun Fang

doi:10.3892/ol.2018.9832

Identification of novel lncRNAs involved in the pathogenesis of childhood acute lymphoblastic leukemia

Oncol Lett. 2019 Feb;17(2):2081-2090. doi: 10.3892/ol.2018.9832. Epub 2018 Dec 14.

Authors

Sheng Li^{1

2}, Hongliang Bian², Yizhi Cao³, Chenxia Juan¹, Qian Cao¹, Guoping Zhou¹, Yongjun Fang⁴

Affiliations

¹ Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
² Department of Pediatrics, Yancheng Maternity and Child Health Care Hospital, Yancheng, Jiangsu 224000, P.R. China.
³ The First Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
⁴ Department of Hematology and Oncology, The Affiliated Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

Abstract

This study aimed to explore novel long non-coding RNAs (lncRNAs) and the underlying mechanisms involved in childhood acute lymphoblastic leukemia (cALL). The GSE67684 dataset was downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) and lncRNAs (DELs) between Days 0, 8, 15 and 33 were isolated using random variance model corrective analysis of variance. Overlapping DEGs and DELs were clustered using Cluster 3.0. Bio-functional enrichment analysis was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Interactions between lncRNAs and mRNAs were calculated using dynamic simulations, and interactions among mRNAs were predicted using the STRING database. lncRNA-mRNA and protein-protein interaction (PPI) networks were visualized using Cytoscape. Subsequently, the expression levels of lncRNAs in biological samples from children with or without cALL were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 593 overlapping DEGs and 21 DELs were identified. After clustering, Profile 26 exhibited a continuously increasing temporal trend, whereas Profile 1 exhibited a continuous decreasing trend. Upregulated DEGs were significantly enriched in 1,825 GO terms and 166 KEGG pathways, whereas downregulated DEGs were significantly enriched in 196 GO terms and 90 KEGG pathways. The lncRNAs NONHSAT027612.2 and NONHSAT134556.2 were the top two regulators in the lncRNA-mRNA network. Toll-like receptor 4, cathepsin G, nucleotide-binding oligomerization domain containing 2 and cathepsin S may be considered the hub genes of the PPI network. RT-qPCR results indicated that the expression levels of the lncRNAs NONHSAT027612.2 and NONHSAT134556.2 were significantly elevated in the blood and bone marrow of patients with cALL compared with the controls. In conclusion, the lncRNAs NONHSAT027612.2 and NONHSAT134556.2 may serve important roles in the pathogenesis of cALL via regulating immune response-associated pathways.

Keywords: childhood acute lymphoblastic leukemia; differentially expressed genes; long non-coding RNA.