scholarly journals Long Noncoding RNA RROL Provides Chromatin Scaffold for MYC-WDR82 Interaction to Impact Lipid Metabolism and Tumor Cell Growth in Multiple Myeloma

2021 ◽  
Author(s):  
Eugenio Morelli ◽  
Mariateresa Fulciniti ◽  
Mehmet Kemal Samur ◽  
Caroline F Ribeiro ◽  
Leon Wert-Lamas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Growth ◽  
Noncoding Rna ◽  
Transcriptional Control ◽  
Myeloma Cell ◽  
Independent Manner ◽  
Functional Activities ◽  
Rate Limiting

Long noncoding RNAs (lncRNA) can drive the tumorigenesis and be susceptible to therapeutic intervention. To define the landscape of therapeutically actionable lncRNA dependencies in multiple myeloma (MM), we coupled our extensive lncRNA transcriptomic profile with lncRNA targeted CRISPR interference viability screen and identified RNA Regulator of Lipogenesis (RROL) as a leading lncRNA dependency in MM. RROL shares its origin with the microRNA locus MIR17HG, however supports the proliferation and survival of MM cells in a microRNA- and DROSHA- independent manner. We found that RROL provides a chromatin scaffold for the functional interaction between c-MYC and WDR82 to promote the regulation of the lipogenic pathways via the transcriptional control of the rate-limiting enzyme ACC1 in MM cells. Inhibition of RROL with clinically applicable antisense molecules disrupts its transcriptional and functional activities causing potent anti-tumor effects both in vitro and in vivo in two pre-clinical animal models. This study establishes lncRNA RROL as a therapeutically actionable dependency with a unique mechanism of action in support of myeloma cell growth.

scholarly journals Interleukin-6 is a potent myeloma-cell growth factor in patients with aggressive multiple myeloma

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 11-13 ◽  
Author(s):  
XG Zhang ◽  
B Klein ◽  
R Bataille
Keyword(s):  
Multiple Myeloma ◽  
Growth Factor ◽  
Cell Growth ◽  
Interleukin 6 ◽  
Myeloma Cell ◽  
S Phase ◽  
Myeloma Cells ◽  
Severity Of The Disease

Abstract It has recently been demonstrated that interleukin-6 (IL-6) is a potent myeloma-cell growth factor in the majority of patients with multiple myeloma (MM). Using an anti-bromodeoxyuridine monoclonal antibody (MoAb) to specifically count myeloma cells in the S-phase (ie, labeling index, LI), we demonstrate that the IL-6 responsiveness of myeloma cells in vitro is directly correlated with their LI in vivo. Myeloma cells from all 13 patients with high LIs in vivo (greater than or equal to 1%) responded in vitro to IL-6, the strongest response occurring in cells from five patients with plasma-cell leukemia. In contrast, the cells of only two of eight patients with low myeloma-cell LIs in vivo (less than 1%) responded to IL-6 in vitro. After seven days of culturing with 1,000 U/mL recombinant IL-6 (rIL-6), the median LI value in the first group of patients (in vivo LI greater than or equal to 1%) was 11%, ie 11 times higher (P less than .01) than the median LI value (1%) in the second group of patients (in vivo LI less than 1%). Thus, the in vitro IL-6 responsiveness of myeloma cells is directly related to their in vivo proliferative status, and hence to the severity of the disease.

scholarly journals Synthetic miR-145 mimic inhibits multiple myeloma cell growth in vitro and in vivo

2014 ◽  
Vol 33 (1) ◽  
pp. 448-456 ◽  
Author(s):  
QI ZHANG ◽  
WEIQUN YAN ◽  
YANG BAI ◽  
HAO XU ◽  
CHANGHAO FU ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Growth ◽  
Myeloma Cell ◽  
Multiple Myeloma Cell

scholarly journals MLN120B, a Novel IκB Kinase β Inhibitor, Blocks Multiple Myeloma Cell Growth In vitro and In vivo

2006 ◽  
Vol 12 (19) ◽  
pp. 5887-5894 ◽  
Author(s):  
Teru Hideshima ◽  
Paola Neri ◽  
Pierfranchesco Tassone ◽  
Hiroshi Yasui ◽  
Kenji Ishitsuka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Growth ◽  
Myeloma Cell ◽  
Multiple Myeloma Cell ◽  
Iκb Kinase

scholarly journals [Retracted] Synthetic miR‑145 mimic inhibits multiple myeloma cell growth in vitro and in vivo

2021 ◽  
Vol 46 (2) ◽  
Author(s):  
Qi Zhang ◽  
Weiqun Yan ◽  
Yang Bai ◽  
Hao Xu ◽  
Changhao Fu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Growth ◽  
Myeloma Cell ◽  
Multiple Myeloma Cell

scholarly journals Targeting miR-21 Inhibits In Vitro and In Vivo Multiple Myeloma Cell Growth

2013 ◽  
Vol 19 (8) ◽  
pp. 2096-2106 ◽  
Author(s):  
Emanuela Leone ◽  
Eugenio Morelli ◽  
Maria T. Di Martino ◽  
Nicola Amodio ◽  
Umberto Foresta ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Growth ◽  
Myeloma Cell ◽  
Multiple Myeloma Cell

scholarly journals Interleukin-6 is a potent myeloma-cell growth factor in patients with aggressive multiple myeloma

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 11-13 ◽  
Author(s):  
XG Zhang ◽  
B Klein ◽  
R Bataille
Keyword(s):  
Multiple Myeloma ◽  
Growth Factor ◽  
Cell Growth ◽  
Interleukin 6 ◽  
Myeloma Cell ◽  
S Phase ◽  
Myeloma Cells ◽  
Severity Of The Disease

It has recently been demonstrated that interleukin-6 (IL-6) is a potent myeloma-cell growth factor in the majority of patients with multiple myeloma (MM). Using an anti-bromodeoxyuridine monoclonal antibody (MoAb) to specifically count myeloma cells in the S-phase (ie, labeling index, LI), we demonstrate that the IL-6 responsiveness of myeloma cells in vitro is directly correlated with their LI in vivo. Myeloma cells from all 13 patients with high LIs in vivo (greater than or equal to 1%) responded in vitro to IL-6, the strongest response occurring in cells from five patients with plasma-cell leukemia. In contrast, the cells of only two of eight patients with low myeloma-cell LIs in vivo (less than 1%) responded to IL-6 in vitro. After seven days of culturing with 1,000 U/mL recombinant IL-6 (rIL-6), the median LI value in the first group of patients (in vivo LI greater than or equal to 1%) was 11%, ie 11 times higher (P less than .01) than the median LI value (1%) in the second group of patients (in vivo LI less than 1%). Thus, the in vitro IL-6 responsiveness of myeloma cells is directly related to their in vivo proliferative status, and hence to the severity of the disease.

Promotion of human multiple myeloma cell growth in vitro and bone marrow invasion in vivo by Notch receptors and the CXCR4/SDF1 axis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8591-8591 ◽  
Author(s):  
Maurizio Chiriva-Internati ◽  
Leonardo Mirandola ◽  
Elisa Lazzari ◽  
Michela Colombo ◽  
Marialuigia Lancellotti ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Drug Resistance ◽  
Cell Growth ◽  
Plasma Cells ◽  
Myeloma Cell ◽  
Notch Receptors ◽  
Associated Lesions

8591 Background: Multiple myeloma (MM) originates from post-germinal center B cells, and is caused by malignant plasma cells accumulating in the bone marrow. Interactions of MM cells with the bone marrow stroma promote tumor growth, migration and drug resistance. The chemokine receptor CXCR4 and its ligand SDF1 are critical regulators of this process. MM cells frequently hyper-express CXCR4 and respond to SDF1,2 enhancing MM cell infiltration, proliferation and osteolysis. Notch receptors similarly promote MM cell growth, drug resistance and the associated osteolytic process. We hypothesized that the CXCR4/SDF1 axis mediates the effects of Notch signals in MM. Methods: We used real-time PCR, flow-cytometry, E.L.I.S.A. and chemotaxis assay to explore the effects of CXCR4 in cultured human MM cell lines after Notch inhibition or over-stimulation. Additionally, we validated our findings in a NOD/SCID murine model xenografted with human MM cells. Results: Our results show that Notch blocking reduced CXCR4 and SDF1 expression by MM cells. Further, Notch activation was required for MM cell chemotactic and proliferative response to SDF1 in vitro. We then investigated the outcome of anti-Notch treatment on human MM cells bone invasion in NOD/SCID mice. Interfering with Notch activity dramatically reduced xenografted MM cell ability to infiltrate the bone marrow, ultimately resulting in diminished tumor burden. Notably, such effect was associated with a decrease of CXCR4 expression. Conclusions: This was the first time that Notch receptors were reported to regulate the CXCR4/SDF1 axis and bone marrow invasion in human MM. These findings indicate that specific Notch-tailored therapies may effectively hamper CXCR4-mediated bone infiltration and associated lesions, and are expected to significantly improve treatment outcome and survival.

scholarly journals Effects of microRNA‑125b on multiple myeloma cell growth in vitro and in vivo

2018 ◽  
Author(s):  
Yanxia Jiang ◽  
Jianghua Ding ◽  
Jing Li ◽  
Guoan Chen
Keyword(s):  
Multiple Myeloma ◽  
Cell Growth ◽  
Myeloma Cell ◽  
Multiple Myeloma Cell

scholarly journals Bone Marrow-Derived Mesenchymal Stromal Cells are Attracted by Multiple Myeloma Cell-Produced Chemokine CCL25 and Favor Myeloma Cell Growth in Vitro and In Vivo

Stem Cells ◽  
2012 ◽  
Vol 30 (2) ◽  
pp. 266-279 ◽  
Author(s):  
Song Xu ◽  
Eline Menu ◽  
Ann De Becker ◽  
Ben Van Camp ◽  
Karin Vanderkerken ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Growth ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Myeloma Cell ◽  
Multiple Myeloma Cell
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