Indirect Tumor Inhibitory Effects of MicroRNA-124 through Targeting EZH2 in The Multiple Myeloma Cell Line
Journal Title: Cell Journal(Yakhteh) - Year 2020, Vol 22, Issue 1
Abstract
Objective: Multiple myeloma (MM) is an incurable plasma cell malignancy. Several genetic and epigenetic changes affect numerous critical genes expression status in this disorder. CDKN2A gene is expressed at low level in almost all cases with MM disease. The mechanism of this gene down-regulation has remained controversial. In the present study, we targeted EZH2 by microRNA-124 (miR-124) in L-363 cells and assessed following possible impact on CDKN2A gene expression and phenotypic changes. Materials and Methods: In this experimental study, growth inhibitory effects of miR-124 were measured by MTT assay in L-363 cell line. Likewise, cell cycle assay was measured by flowcytometery. The expression levels of EZH2 and CDKN2A were evaluated by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results: qRT-PCR results showed induction of EZH2 gene expression after transduction of cells with lentivector expressing miR-124. The expression of CDKN2A was also upregulated as the result of EZH2 supression. Coincide with gene expression changes, cell cycle analysis by flow-cytometry indicated slightly increased G1-arrest in miRtransduced cells (P<0.05). MTT assay results also showed a significant decrease in viability and proliferation of miRtransduced cells (P<0.05). Conclusion: It seems that assembling of H3K27me3 mark mediated by EZH2 is one of the key mechanisms of suppressing CDKN2A gene expression in MM disease. However, this suppressive function is applied by a multi-factor mechanism. In other words, targeting EZH2, as the core functional subunit of PRC2 complex, can increase expression of the downstream suppressive genes. Consequently, by increasing expression of tumor suppressor genes, myeloma cells are stopped from aberrant expansions and they become susceptible to regulated cellular death.
Authors and Affiliations
Javid Sabour Takanlu, Arad Aghaie Fard, Saeed Mohammdi, Seyed Mohammad Ali Hosseini Rad, Saeid Abroun, Mohsen Nikbakht
Keywords
Related Articles
- EP ID EP637383
- DOI 10.22074/cellj.2020.6492
- Views 202
- Downloads 0
The Study of rs693 and rs515135 in APOB in People with Familial Hypercholestrolemia
Objective APOB-related familial hypercholesterolemia (FH) is the most common hereditary hyperchlosterolemia with an autosomal dominant pattern. A number of APOB variants are the most important risk factors for hyperchlos...
FACT or PACT: A Comparison between Free-Acrylamide and Acrylamide-Based Passive Sodium Dodecyl Sulfate Tissue Clearing for whole Tissue Imaging
Major biological processes rely on the spatial organization of cells in complex, highly orchestrated three-dimensional (3D) tissues. Until the recent decade, most of information on spatial neural representation primarily...
A Review on Various Uses of N-Acetyl Cysteine
N-acetyl cysteine (NAC), as a nutritional supplement, is a greatly applied antioxidant in vivo and in vitro. NAC is a precursor of L-cysteine that results in glutathione elevation biosynthesis. It acts directly as a scav...
Melatonin Modifies Histone Acetylation during In Vitro Maturation of Mouse Oocytes
Objective: We evaluated the effect of melatonin, as a potent antioxidant agent, on glutathione (GSH) and reactive oxygen species (ROS) levels, as well as histone H3 lysine 9 (H3K9), and H4 lysine 12 (H4K12) acetylation w...
The Important Role of FLT3-L in Ex Vivo Expansion of Hematopoietic Stem Cells following Co-Culture with Mesenchymal Stem Cells
Objective: Hematopoietic stem cells (HSCs) transplantation using umbilical cord blood (UCB) has improved during the last decade. Because of cell limitations, several studies focused on the ex vivo expansion of HSCs. Nume...