Long Non-coding RNAs in the Pathophysiology of Multiple Myeloma: New Insights on the Role of CRNDE

Simone Zocchi ,Antoine David ,Michele Goodhardt ,David Garrick

doi:10.33696/cancerimmunol.3.036

Abstract

Over the past 15 years, long non-coding RNAs (lncRNA) have emerged as an important class of regulatory molecules.The currently accepted definition is that lncRNA refers to RNA molecules with little or no protein-coding potential, and which are greater than 200 nucleotides in length, a size cut-off chosen largely to distinguish them from the more-extensively characterised group of small non-coding regulatory RNAs, which includes micro (mi)RNAs, small inhibitory (si)RNAs and PIWI-interacting (pi)RNAs.

Highlights

Over the past 15 years, long non-coding RNAs have emerged as an important class of regulatory molecules
The currently accepted definition is that long non-coding RNAs (lncRNA) refers to RNA molecules with little or no protein-coding potential, and which are greater than 200 nucleotides in length, a size cut-off chosen largely to distinguish them from the more-extensively characterised group of small non-coding regulatory RNAs, which includes microRNAs, small inhibitoryRNAs and PIWI-interactingRNAs [1]
The altered expression of lncRNAs can lead to downstream changes in a variety of cancerassociated pathways, including dysregulation of p53 and other cell signalling pathways, control of hypoxia and the Endothelial-Mesenchymal Transition (EMT) as well as epigenetic dysregulation [10]

Summary

Long Noncoding RNAs in Multiple Myeloma

Over the past 15 years, long non-coding RNAs (lncRNA) have emerged as an important class of regulatory molecules. Among the few lncRNAs which have been extensively investigated in MM, important examples include the well-established oncogenic lncRNAs MALAT1, H19, TUG1, UCA1 as well as the known tumoursuppressor lncRNA MEG3 (for recent reviews see [21,22,23]) These studies revealed that lncRNAs often affect MM cell growth and tumour progression by different pathways to those observed in other malignancies, suggesting that the molecular mechanisms involved are likely to be disease- and context-dependent. Expression of CRNDE correlated with that of IL6R in our cohort of primary tumour plasma cells, supporting the idea that increased levels of CRNDE leads to transcriptional activation of the IL6R gene in MM patients [24] Together these observations indicate that CRNDE impacts upon MM progression and outcome by sensitizing malignant plasma cells to pro-tumorigenic IL6 signalling due to enhanced levels of the IL6 receptor (Figure 1B)

Bone marrow stromal cells

Findings

Future Perspectives