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Mir-186 inhibits the proliferation and growth of multiple myeloma cells by targeting Jagged-1 expression
Abstract
Purpose: To investigate the suppressive influence of mir-186 on multiplication and growth of multiple myeloma (MM), as well as the processes involved.
Methods: The U266 cells were divided into control, mir-186 overexpression, and inhibition groups. The latter two were transfected with mir-186 agent and antagonist, respectively. Cell viability, colony formation potential, cell cycle ratio, and Jagged-1 mRNA and protein levels were measured using various assays.
Results: Cell growth increased over time in all groups. However, mir-186 overexpression cells showed significantly decreased growth and colony formation capacity, relative to control, while the mir-186 inhibition cells showed significantly higher growth and colony formation capacity. The study revealed a higher proportion of G0/G1 stage cells and lower proportion of S-phase cells in mir-186 overexpression cells than in control cells. The opposite effect was seen in mir-186 inhibition cells. Jagged-1 protein and mRNA levels were significantly lower in mir-186 overexpression cells and higher in mir-186 inhibition cells than in control group. The Jagged-1 knockout group showed significantly higher Jagged-1 mRNA and protein levels than both the control and mir-186 overexpression groups (p < 0.05).
Conclusion: When overexpressed, mir-186 inhibits the growth of multiple myeloma cells by inhibiting cell colony-formation capacity and by regulating cell cycle through mir-186-induced regulation of the expression of Jagged-1. there is need for more research to confirm the clinical benefits of therapies based on these findings.