Dataset Information

LncRNAs-mRNAs Co-Expression Network Underlying Childhood B-Cell Acute Lymphoblastic Leukaemia: A Pilot Study.

ABSTRACT: Long non-coding RNAs (lncRNAs) are emerging as key gene regulators in the pathogenesis and development of various cancers including B lymphoblastic leukaemia (B-ALL). In this pilot study, we used RNA-Seq transcriptomic data for identifying novel lncRNA-mRNA cooperative pairs involved in childhood B-ALL pathogenesis. We conceived a bioinformatic pipeline based on unsupervised PCA feature extraction approach and stringent statistical criteria to extract potential childhood B-ALL lncRNA signatures. We then constructed a co-expression network of the aberrantly expressed lncRNAs (30) and protein-coding genes (754). We cross-validated our in-silico findings on an independent dataset and assessed the expression levels of the most differentially expressed lncRNAs and their co-expressed mRNAs through ex vivo experiments. Using the guilt-by-association approach, we predicted lncRNA functions based on their perfectly co-expressed mRNAs (Spearman's correlation) that resulted closely disease-associated. We shed light on 24 key lncRNAs and their co-expressed mRNAs which may play an important role in B-ALL pathogenesis. Our results may be of clinical utility for diagnostic and/or prognostic purposes in paediatric B-ALL management.

SUBMITTER: Affinito O

PROVIDER: S-EPMC7564554 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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lncRNAs-mRNAs Co-Expression Network Underlying Childhood B-Cell Acute Lymphoblastic Leukaemia: A Pilot Study.

Affinito Ornella O Pane Katia K Smaldone Giovanni G Orlandella Francesca Maria FM Mirabelli Peppino P Beneduce Giuliana G Parasole Rosanna R Ripaldi Mimmo M Salvatore Marco M Franzese Monica M

Cancers 20200902 9

Long non-coding RNAs (lncRNAs) are emerging as key gene regulators in the pathogenesis and development of various cancers including B lymphoblastic leukaemia (B-ALL). In this pilot study, we used RNA-Seq transcriptomic data for identifying novel lncRNA-mRNA cooperative pairs involved in childhood B-ALL pathogenesis. We conceived a bioinformatic pipeline based on unsupervised PCA feature extraction approach and stringent statistical criteria to extract potential childhood B-ALL lncRNA signatures. ...[more]

PMID: 32887470

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Project description: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.

Dataset Information

LncRNAs-mRNAs Co-Expression Network Underlying Childhood B-Cell Acute Lymphoblastic Leukaemia: A Pilot Study.

Publications

lncRNAs-mRNAs Co-Expression Network Underlying Childhood B-Cell Acute Lymphoblastic Leukaemia: A Pilot Study.

Similar Datasets

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