Identification of ceRNA Regulatory Networks Driven by the lncRNA NEAT1 in Multiple Myeloma

ABSTRACT The lncRNA NEAT1 is overexpressed in multiple myeloma (MM) plasma cells and plays a key role in MM pathogenesis. NEAT1 is involved in ceRNA network in several cancers; however, data in MM are virtually absent. This study identified a NEAT1‐driven ceRNA network involving 96 miRNAs and 40 target genes, selected as concurrently downregulated in NEAT1‐KD AMO1 cells and upregulated in NEAT1‐overexpressing AMO1 cells (AMO1‐OVX). The co‐expression of NEAT1 and the targets was validated in MM patients (GSE116294, GSE13591, GSE6477, CoMMpass), and in NEAT1‐KD NCI‐H929, LP1, and KMS27 cell lines, showing for all targets a consistent downregulation, resembling that of NEAT1. The functional implication of the ceRNA network was explored by functional enrichment analyses of the 40 targets, identifying 78 significant gene sets, 17 of which were found significantly enriched by GSEA analysis in at least one experimental condition among NEAT1‐KD LP1, NCI‐H929, and KMS27 cells, AMO1‐OVX cells, or the extreme quartiles of NEAT1 expression in the CoMMpass dataset. Noteworthy, the cell cycle gene set was validated in 5 out of 6 conditions tested, suggesting that in MM the impact of NEAT1 upregulation on the cell cycle, experimentally demonstrated in our earlier publications, may be attributable, at least partially, to ceRNA mechanisms.