The expression of MALAT1 long non-coding RNA is associated with good prognosis in mantle cell lymphoma

MALAT1 is a long non-coding RNA (lncRNA) with altered expression in many cancers but poorly studied in B-cell neoplasms like mantle cell lymphoma (MCL), a very aggressive B-cell lymphoma. To elucidate the role of MALAT1 in MCL we have investigated its expression in 219 primary tumors using microarray data. We also analyzed the expression of its natural antisense transcript (TALAM1), which is key for the processing of MALAT1 RNA to its active isoform. High expression of MALAT1/TALAM1 lncRNAs was consistently linked to favorable clinical behavior in MCL, independently of other alterations previously described to influence MCL prognosis. In concordance with the observed clinical association, we found that the increased expression of these lncRNAs was inversely associated with gene signatures related to a proliferative and activation phenotype (MCL35-proliferation/BCR signaling signatures) in MCL samples from lymph nodes as peripheral blood. Finally, functional studies of MALAT1 in MCL primary samples showed that its levels were downregulated by microenvironmental stimuli and EZH2 activity, a known epigenetic factor induced by pro-proliferative stimuli and previously related with poor MCL prognosis. Altogether, these data support the favorable prognostic value of MALAT1 expression in MCL, and the MALAT1 dual role as oncogene or tumor suppressor in different neoplasms.