scholarly journals Activation of Mammalian Target of Rapamycin Signaling Promotes Cell Cycle Progression and Protects Cells from Apoptosis in Mantle Cell Lymphoma

2006 ◽  
Vol 169 (6) ◽  
pp. 2171-2180 ◽  
Author(s):  
Evangelia Peponi ◽  
Elias Drakos ◽  
Guadalupe Reyes ◽  
Vasiliki Leventaki ◽  
George Z. Rassidakis ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mantle Cell Lymphoma ◽  
Cell Cycle Progression ◽  
Cell Lymphoma ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Cycle Progression ◽  
Mantle Cell

Discovery and Design of Peptides as MMP9 Inhibitors through StructureBased Molecular Docking for Targeted Mantle Cell Lymphoma Therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Wei Yan ◽  
Ying Yang ◽  
Wei Yang ◽  
Minjie Wei
Keyword(s):  
Cell Cycle ◽  
Molecular Docking ◽  
Mantle Cell Lymphoma ◽  
Cell Cycle Progression ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Migration And Invasion ◽  
Cycle Progression ◽  
Mmp9 Expression ◽  
Mantle Cell

Background: Enhanced expression and activation of metalloproteinase-9 (MMP9) is associated with mantle cell lymphoma (MCL) progression, invasion and metastasis. Objective: To find potential peptide inhibitor against MMP9, which in turn, could inhibit MCL progression. Methods: We performed CCK8 assay, western blot and transwell assays for RNAi activity. Molecular Operating Environment (MOE) software was applied for structural optimization as MMP9 and peptides were docked. We used gelatin zymography and confocal microscopy confirm that the peptides can inhibit MMP9 activity. We applied CCK8 and transwell assay to evaluate cell proliferation and metastasis and flow cytometry to evaluate cell cycle progression and apoptosis. Results: High MMP9 expression was observed in 49 of 88 samples (55.7%). Patients with high MMP9 expression were more likely to present with high stage (Stage 3-4, P=0.01), bone marrow invasion (P=0.033) and high level LDH (P=0.000). High MMP9 expression was associated with significantly shorter overall survival (OS, HR=2.378, P=0.012) and progression free survival (PFS, HR=2.068, P=0.03). Multivariate analysis identified high MMP9 expression (P= 0.027), high-risk mantle cell lymphoma international prognostic index (MIPI, HR=2.327, P=0.023), and no radiation therapy (P=0.035) as adverse prognostic factors. Silencing of MMP9 in Jeko-1 cells by RNAi suppressed cells migration and invasion in vitro (P<0.05). According to the docking results, peptide M3 bound deeply in the binding pocket of MMP9 and had interaction with the active-site Zn2+ ion in the catalytic domain. M3 was not only compatible with MMP9, but also inhibited its activity. M3 inhibited Jeko-1 cells proliferation, metastasis and cell cycle progression, and promoted cell apoptosis rate (P<0.05). Conclusion: We designed M3 through structure-based molecular docking, which can specifically bind to MMP9 and inhibit the activity of MMP9. M3 could be a potential antagonist as the treatment of MCL with MMP9 overexpression.

scholarly journals Rational targeted therapies to overcome microenvironment-dependent expansion of mantle cell lymphoma

Blood ◽  
2016 ◽  
Vol 128 (24) ◽  
pp. 2808-2818 ◽  
Author(s):  
David Chiron ◽  
Céline Bellanger ◽  
Antonin Papin ◽  
Benoit Tessoulin ◽  
Christelle Dousset ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Drug Resistance ◽  
Cell Cycle Progression ◽  
Cell Lymphoma ◽  
Cycle Progression ◽  
Key Points ◽  
Mantle Cell ◽  
Molecular Profiles

Key Points CD40L plus cytokines induces cell-cycle progression and loss of mitochondrial priming, leading to drug resistance in MCL. CD40L plus cytokines mimics in situ molecular profiles and allows the development of new approaches by integrating the role of the microenvironment.

scholarly journals Truncation in CCND1 mRNA alters miR-16-1 regulation in mantle cell lymphoma

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 822-829 ◽  
Author(s):  
Robert W. Chen ◽  
Lynne T. Bemis ◽  
Carol M. Amato ◽  
Han Myint ◽  
Hung Tran ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Binding Sites ◽  
Cell Cycle Progression ◽  
Cell Lymphoma ◽  
Phase Cell ◽  
Cycle Progression ◽  
New Class ◽  
Mantle Cell ◽  
Posttranscriptional Level

Abstract Cyclin D1 (CCND1) is a well-known regulator of cell-cycle progression. It is overexpressed in several types of cancer including breast, lung, squamous, neuroblastoma, and lymphomas. The most well-known mechanism of overexpression is the t(11;14)(q13;q32) translocation found in mantle cell lymphoma (MCL). It has previously been shown that truncated CCND1 mRNA in MCL correlates with poor prognosis. We hypothesized that truncations of the CCND1 mRNA alter its ability to be down-regulated by microRNAs in MCL. MicroRNAs are a new class of abundant small RNAs that play important regulatory roles at the posttranscriptional level by binding to the 3′ untranslated region (UTR) of mRNAs blocking either their translation or initiating their degradation. In this study, we have identified the truncation in CCND1 mRNA in MCL cell lines. We also found that truncated CCND1 mRNA leads to increased CCND1 protein expression and increased S-phase cell fraction. Furthermore, we demonstrated that this truncation alters miR-16-1 binding sites, and through the use of reporter constructs, we were able to show that miR-16-1 regulates CCND1 mRNA expression. This study introduces the role of miR-16-1 in the regulation of CCND1 in MCL.

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