Abstract
Purpose: To determine the effect of miR-379 in multiple myeloma.Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the expression of miR-379 in multiple myeloma cells. The effect of miR-379 on multiple myeloma progression was investigated by cell counting, bromodeoxyuridine staining, flow cytometry and Western blot analysis. A potential target for miR-379 was determined using a luciferase reporter assay.Results: MiR-379 expression was reduced in multiple myeloma cells, while over-expression of miR-379 increased both cell viability and proliferation of these cells (p < 0.05). Moreover, miR-379 blocked cell cycle multiple myeloma cells and promoted apoptosis by decreasing Bcl-2 expression, and increasing the expression of cleaved caspase-3 and Bax. MiR-379 bound to Y-box binding protein 1 (YBX1) and reduced YBX1 mRNA and protein expression in multiple myeloma cells (p < 0.05).Conclusion: A YBX1-mediated tumor-suppressive role for miR-379 in multiple myeloma cells has been identified, suggesting a potential strategy for the treatment of multiple myeloma.
 Keywords: MiR-379, Y-box binding protein 1, Multiple myeloma, Proliferation, Apoptosis
Highlights
Multiple myeloma is a common malignancy of the blood system, usually occurring in middle-aged and elderly individuals [1]
For the determination of miR-379 differential expression in multiple myeloma cells, three human multiple myeloma cell types, RPMI-8226, NCI-H929, and U266 were used for Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis
The analysis showed a significant reduction in miR-379 expression in multiple myeloma cells compared to normal bone marrowderived plasma cells (nPCs) (p
Summary
Multiple myeloma is a common malignancy of the blood system, usually occurring in middle-aged and elderly individuals [1]. The present study investigated the anticancer role of miR-379 in multiple myeloma, and determined the potential miR-379-YBX1 network involved in tumor progression. RPMI-8226 and NCI-H929 cells were incubated with 100 nM bromodeoxyuridine (Sigma-Aldrich, St. Louis, MO, USA) for 4 h before fixation using paraformaldehyde. To investigate the role of miR-379 in multiple myeloma, RPMI-8226 and NCI-H929 cells were transfected with miR-379 mimics (Figure 2A), and significant decreases in cell viability were detected for these cells compared to the NC mimic group (Figure 2B). A decrease in bromodeoxyuridine incorporation in RPMI8226 and NCI-H929 cells transfected with miR379 mimics indicated that miR-379 repressed multiple myeloma cell proliferation (Figure 2C). MiR-379 blocked the cell cycles of RPMI-8226 and NCI-H929 cells at the G0/G1 phase (Figure 3), demonstrating an antiproliferative effect of miR-379 on multiple myeloma.
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