Post-transcriptional Modifications Contribute to the Upregulation of Cyclin D2 in Multiple Myeloma

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Irena Misiewicz-KrzeminskaNorma C Gutiérrez

Abstract

Dysregulation of one of the three D-cyclin genes has been observed in virtually all multiple myeloma tumors. The mechanisms by which CCND2 is upregulated in a set of multiple myeloma are not completely deciphered. We investigated the role of post-transcriptional regulation through the interaction between miRNAs and their binding sites at 3'UTR in CCND2 overexpression in multiple myeloma. Eleven myeloma cell lines and 45 primary myeloma samples were included in the study. Interactions between miRNAs deregulated in multiple myeloma and mRNA targets were analyzed by 3'UTR-luciferase plasmid assay. The presence of CCND2 mRNA isoforms different in length was explored using qRT-PCR, Northern blot, mRNA FISH, and 3' rapid amplification of cDNA ends (RACE)-PCR. We detected the presence of short CCND2 mRNA, both in the multiple myeloma cell lines and primary cells. The results obtained by 3'RACE experiments revealed that changes in CCND2 3'UTR length are explained by alternative polyadenylation. The luciferase assays using plasmids harboring the truncated CCND2 mRNA strongly confirmed the loss of miRNA sites in the shorter CCND2 mRNA isoform. Those multiple myelomas with greater abundance of the shorter 3'UTR isoform were associated wit...Continue Reading

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Citations

Aug 17, 2016·Disease Markers·A Quintanal-VillalongaS Molina-Pinelo
Jan 19, 2019·Non-coding RNA·Irena Misiewicz-KrzeminskaNorma C Gutiérrez
Nov 2, 2018·Blood Advances·Hidemasa MatsuoSouichi Adachi
Feb 11, 2021·Cells·Ignacio J Cardona-BenavidesNorma C Gutiérrez
May 1, 2021·International Journal of Molecular Sciences·Nikolaos GiannakoulasEvangelos Terpos
Sep 29, 2021·Wiley Interdisciplinary Reviews. RNA·Neeraja K MohananRakesh S Laishram

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