Transcriptome analysis of the lncRNAs and their mRNA networks associated with multiple myeloma

Abstract

BackgroundTo study the lncRNA-mRNA interaction network structure and analyze the possible target mRNAs among the differentially expressed lncRNAs between healthy adults, newly diagnosed multiple myeloma patients, and refractory relapsed multiple myeloma patients.MethodsPublic sequence data files were downloaded from the Sequence Read Archive (SRA). Totally 23 RNA-seq samples (GSE110486) related to myeloma published in 2018 (including transcriptome data of bone marrow plasma cells from healthy adults, newly diagnosed multiple myeloma patients and recurrent patients) were acquired, further analyses of differential lncRNAs, lncRNAs-mRNA co-expression, and WGCNA expression module and cis regulatory gene were performed. In addition, we performed differential expression analysis of lncRNAs and enrichment analysis of target mRNA regulated by lncRNAs from multiple myeloma patients and healthy controls which in order to verify the functions of these lncRNAs and their target mRNAs.ResultsFrom the transcriptional samples in this study,1006 new lncRNAs were identified, which including 707 lncRNAs specifically up-regulated and 283 specifically down-regulated in relapsed myeloma. The mRNA genes co-expressed with specific lncRNAs in relapsed multiple myeloma were mainly enriched in the extracellular matrix organization, platelet activation, cell adhesion, inflammation response, T cell co-stimulation and immune response pathways. Target mRNA regulated by DE lncRNAs including IL23R, ELF3, IL32, TMIGD2, CD28, CD5, TNF, CX3CR1, ADAMTS20 etc, by GO analysis, these target genes were enriched into many biological processes, such as innate immunity, apoptosis and positive regulation of apoptosis. The cis-regulated lncRNA of these target mRNAs include U62631.5, XLOC_062939 and XLOC_027240, and their cis-regulatory targets include CD22, SSX1 and DCC. lncRNAs and enrichment analysis of target mRNA regulated by lncRNAs from multiple myeloma patients and healthy controls was consistent with the previous analysis.ConclusionTarget mRNAs regulated by DE lncRNAs and their cis-regulatory targets are involved in the immune cells remodeling of gene expression patterns during multiple myeloma relapse, and may have an important function in this pathological process, it deserves further study as a potential target for the treatment of multiple myeloma.