Indirect Tumor Inhibitory Effects of MicroRNA-124 through Targeting EZH2 in The Multiple Myeloma Cell Line

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Sabour Takanlu Javid; Aghaie Fard Arad; MOHAMMADI SAEED; Hosseini Rad Seyed Mohammad Ali; ABROUN SAEID; NIKBAKHT MOHSEN

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Journal: Cell Journal (Yakhteh) Year:2020 | Volume:22 | Issue:1 Page(s): 23-29

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Title

Indirect Tumor Inhibitory Effects of MicroRNA-124 through Targeting EZH2 in The Multiple Myeloma Cell Line

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Keywords

Cyclin-Dependent Kinase Inhibitor 2A

Enhancer of Zeste Homolog 2

Multiple Myeloma

MicroRNA

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.

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APA: Copy

Sabour Takanlu, Javid, Aghaie Fard, Arad, MOHAMMADI, SAEED, Hosseini Rad, Seyed Mohammad Ali, ABROUN, SAEID, & NIKBAKHT, MOHSEN. (2020). Indirect Tumor Inhibitory Effects of MicroRNA-124 through Targeting EZH2 in The Multiple Myeloma Cell Line. CELL JOURNAL (YAKHTEH), 22(1), 23-29. SID. https://sid.ir/paper/730584/en

Vancouver: Copy

Sabour Takanlu Javid, Aghaie Fard Arad, MOHAMMADI SAEED, Hosseini Rad Seyed Mohammad Ali, ABROUN SAEID, NIKBAKHT MOHSEN. Indirect Tumor Inhibitory Effects of MicroRNA-124 through Targeting EZH2 in The Multiple Myeloma Cell Line. CELL JOURNAL (YAKHTEH)[Internet]. 2020;22(1):23-29. Available from: https://sid.ir/paper/730584/en

IEEE: Copy

Javid Sabour Takanlu, Arad Aghaie Fard, SAEED MOHAMMADI, Seyed Mohammad Ali Hosseini Rad, SAEID ABROUN, and MOHSEN NIKBAKHT, “Indirect Tumor Inhibitory Effects of MicroRNA-124 through Targeting EZH2 in The Multiple Myeloma Cell Line,” CELL JOURNAL (YAKHTEH), vol. 22, no. 1, pp. 23–29, 2020, [Online]. Available: https://sid.ir/paper/730584/en

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