Long-chain non-coding RNA MALAT1 regulates paclitaxel resistance of breast cancer cells by targeting miR-485-3p / 南方医科大学学报

ABSTRACT

OBJECTIVE@#To investigate the role of long-chain non-coding RNA MALAT1 in modulating paclitaxel resistance in breast cancer cells.@*METHODS@#Breast cancer SK-BR-3 cells were treated with gradient concentrations of paclitaxel to induce paclitaxel resistance of the cells. The resistant cells were transfected with si-NC, si-MALAT1, pcDNA, pcDNA-MALAT1, miRNC, miR-485-3p mimics, si-MALAT1+anti-miR-NC, or si-MALAT1+anti-miR-485-3p liposomes. Following the transfections, the cells were examined for changes in IC of paclitaxel using MTT assay; the protein expression of P-gp, Bcl-2 and Bax were detected with Western blotting, and a dual luciferase reporter assay was used to detect the binding of MALAT1 to miR-485-3p.@*RESULTS@#Compared with paclitaxel-sensitive SK-BR-3 cells, paclitaxel-resistant SK-BR-3 cells showed significantly increased the IC of paclitaxel with up-regulated MALAT1 expression and down-regulated miR-485-3p expression ( < 0.05). Silencing MALAT1 or overexpressing miR-485-3p obviously lowered the IC of paclitaxel and the expression of P-gp and Bcl-2 and increased the expression of Bax in SK-BR-3/PR cells ( < 0.05). miR-485-3p was identified as the target of MALAT1, and inhibiting miR-485-3p significantly reverse the effect of MALAT1 silencing on IC of paclitaxel and the expressions of P-gp, Bcl-2 and Bax in SK-BR-3/PR cells ( < 0.05).@*CONCLUSIONS@#MALAT1 can modulate paclitaxel resistance in breast cancer cells possibly by targeting miR-485-3p to down-regulate P-gp and Bcl-2 and up-regulate Bax.