Abstract
BackgroundLong non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides (nt) that are involved in the pathogenesis and development of various cancers including B cell acute lymphoblastic leukemia (B–ALL). To determine the potential roles of lncRNAs involved in pathogenesis of B-ALL, we analyzed the expression profile of lncRNAs and mRNAs in B-ALL, respectively, and constructed lncRNAs/mRNAs interaction network.MethodsWe performed RNA sequencing of 10 non-leukemic blood disease donors and 10 B-ALL patients for Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Interactions among mRNAs were predicted using the STRING database. Quantitative real time PCR (qRT-PCR) was performed to verify the RNA-seq data of lncRNAs and mRNAs. Potential functions of subtype-specific lncRNAs were determined by using coexpression-based analysis on distally (trans-pattern) located protein-coding genes.ResultsA total of 1813 differentially expressed transcripts (DETs) and 2203 lncRNAs were identified. Moreover, 10 dysregulated lncRNAs and 10 mRNAs were randomly selected, and further assessed by RT-qPCR in vitro. Go and KEGG analysis demonstrated that the differentially expressed mRNAs were most closely associated with myeloid leukocyte activation and in transcriptional misregulation in cancer, respectively. In addition, co-expression analysis demonstrated that these lncRNAs, including MSTRG.27994.3, MSTRG.21740.1, ENST00000456341, MSTRG.14224.1 and MSTRG.20153.1, may mediate the pathogenesis and development of B-ALL via lncRNA-mRNA network interactions.ConclusionsThese results showed that several mRNAs and lncRNAs are aberrantly expressed in the bone marrow of B-ALL patients and play potential roles in B-ALL development, and be useful for diagnostic and/or prognostic purposes in pediatric B–ALL.Data availabilityThe datasets used during our study are available through HARVARD Dataverse Persistent ID doi:https://doi.org/10.7910/DVN/LK9T4Z.
Highlights
Long non-coding RNAs are transcripts longer than 200 nucleotides that are involved in the pathogenesis and development of various cancers including B cell acute lymphoblastic leukemia (B–Acute lymphoblastic leukemia (ALL))
According to the position relation of Long non-coding RNA (lncRNA) and adjacen messenger RNA (mRNA), lncRNAs were classified into six categories: 47.0% were intergenic, 11.2% were antisense, 32.6% were sense, 3.0% were intronic, 4.4% were bidirectional, and 1.8% were others (Fig. S2B)
In-depth analysis showed that 16 lncRNAs and 2 mRNAs (IGKV1OR2–108 and IRX2) were significantly upregulated > 10(Log2FC) in B cell acute lymphoblastic leukemia (B-ALL)
Summary
Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides (nt) that are involved in the pathogenesis and development of various cancers including B cell acute lymphoblastic leukemia (B–ALL). The lncRNA CRNDE has been shown to upregulate CREB expression by suppressing miR-345-5p, promoting cell proliferation, and reducing cell apoptosis in ALL [10, 11]. All of these above studies indicate that lncRNAs could affect the expression of mRNAs via co-expression networks. Specific focus was given to differential mRNA and lncRNA expression levels and lncRNAmRNA networks to identify the potential underlying mechanism of B-ALL. This approach may provide novel insights into further functional studies, and may reveal new biomarkers for the diagnosis of B-ALL
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