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Inhibition of DEPDC1A, a Bad Prognostic Marker in Multiple Myeloma, Delays Growth and Induces Mature Plasma Cell Markers in Malignant Plasma Cells

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Journal PLoS One
Date 2013 May 7
PMID 23646139
Citations 15
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Abstract

High throughput DNA microarray has made it possible to outline genes whose expression in malignant plasma cells is associated with short overall survival of patients with Multiple Myeloma (MM). A further step is to elucidate the mechanisms encoded by these genes yielding to drug resistance and/or patients' short survival. We focus here on the biological role of the DEP (for Disheveled, EGL-10, Pleckstrin) domain contained protein 1A (DEPDC1A), a poorly known protein encoded by DEPDC1A gene, whose high expression in malignant plasma cells is associated with short survival of patients. Using conditional lentiviral vector delivery of DEPDC1A shRNA, we report that DEPDC1A knockdown delayed the growth of human myeloma cell lines (HMCLs), with a block in G2 phase of the cell cycle, p53 phosphorylation and stabilization, and p21(Cip1) accumulation. DEPDC1A knockdown also resulted in increased expression of mature plasma cell markers, including CXCR4, IL6-R and CD38. Thus DEPDC1A could contribute to the plasmablast features of MMCs found in some patients with adverse prognosis, blocking the differentiation of malignant plasma cells and promoting cell cycle.

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References
1.
Lemee F, Bergoglio V, Fernandez-Vidal A, Machado-Silva A, Pillaire M, Bieth A . DNA polymerase theta up-regulation is associated with poor survival in breast cancer, perturbs DNA replication, and promotes genetic instability. Proc Natl Acad Sci U S A. 2010; 107(30):13390-5. PMC: 2922118. DOI: 10.1073/pnas.0910759107. View

2.
Greipp P, Leong T, Bennett J, Gaillard J, Klein B, Stewart J . Plasmablastic morphology--an independent prognostic factor with clinical and laboratory correlates: Eastern Cooperative Oncology Group (ECOG) myeloma trial E9486 report by the ECOG Myeloma Laboratory Group. Blood. 1998; 91(7):2501-7. View

3.
Medugno L, Florio F, De Cegli R, Grosso M, Lupo A, Costanzo P . The Krüppel-like zinc-finger protein ZNF224 represses aldolase A gene transcription by interacting with the KAP-1 co-repressor protein. Gene. 2005; 359:35-43. DOI: 10.1016/j.gene.2005.06.021. View

4.
Harada Y, Kanehira M, Fujisawa Y, Takata R, Shuin T, Miki T . Cell-permeable peptide DEPDC1-ZNF224 interferes with transcriptional repression and oncogenicity in bladder cancer cells. Cancer Res. 2010; 70(14):5829-39. DOI: 10.1158/0008-5472.CAN-10-0255. View

5.
Pillaire M, Selves J, Gordien K, Gourraud P, Gouraud P, Gentil C . A 'DNA replication' signature of progression and negative outcome in colorectal cancer. Oncogene. 2009; 29(6):876-87. DOI: 10.1038/onc.2009.378. View