Deregulated high expression of NEAT1 lncRNA in multiple myeloma is unrelated to molecular features and clinical outcome

Multiple myeloma (MM) is a malignant proliferation of bone marrow plasma cells, whose pathogenesis remains largely unknown. Long ncRNAs (lncRNAs) are a large class of non-protein-coding RNA, involved in many physiological cellular and genomic processes as well as in carcinogenesis, cancer metastasis and invasion. The biological role and therapeutic potential of lncRNAs in MM are still to be explored. Herein, we investigated the nuclear paraspeckle assembly transcript 1 (NEAT1) in the context of plasma cell dyscrasia, in a cohort of 50 MM and 15 plasma cell leukemia samples. Array expression data indicated that NEAT1 was upregulated in tumor samples compared to four healthy controls. Moreover, in MM patients, NEAT1 was globally overexpressed irrespectively of molecular characteristic, as further supported by Q-RT-PCR validation and by RNA sequencing data in a representative subgroup of cases. The functional annotation of genes and the lncRNAs transcriptional signature associated with NEAT1 expression indicated the modulation of DNA repair and metabolism, dynein interaction and unfolded protein response pathways. We tested NEAT1 clinical relevance in a retrospective proprietary dataset including 55 MM and in the large TT2/TT3 trials cohort from the University of Arkansas encompassing more than 550 patients; in both cases, NEAT1 overexpression was not correlated with patient’s prognosis. Total RNA samples from highly purified plasma cells of 50 MM cases at onset, 15 plasma cell leukemia and 4 normal controls (purchased from Voden, Medical Instruments IT). 30 MM and 4 N samples in common with GSE109116.