[MicroRNA-138 regulates cell adhesion-mediated drug resistance phenotype by targeting SGTA in non-Hodgkin's lymphoma].

To analyze the effects of miR-138 on the expression of small glutamine-rich TPR-containing protein A (SGTA) and cell adhesion-mediated drug resistance (CAM-DR) phenotype in non-Hodgkin's lymphoma (NHL). The adhesion model was constructed using fibronectin (FN) or bone marrow stromal cells HS-5. The effect of miR-138 on the expression of SGTA was analyzed by Western blotting and RQ-PCR. Dual-luciferase assays were performed to probe the effects of miR-138 on SGTA 3' UTR activities. Subsequently, we investigated the effect of miR-138 on cell cycle, adhesion ability and CAM-DR. Moreover, the correlation between miR-138 expression and therapeutic response was analyzed in 35 paraffin-embedded diffuse large B cell lymphoma samples. Our data showed that adhesion of NHL cells to FN or HS-5 cells significantly increased miR-138 expression (<0.05). Knockdown of miR-138 markedly increased the protein (all <0.05) but not for mRNA (all >0.05) levels of SGTA in NHL cell. The luciferase activity of SGTA 3' UTR was significantly suppressed by miR-138 transfected cells (0.73±0.03 1.00±0.02, =0.914, =0.002). No change in terms of reporter activity was observed in SGTA 3'UTR mutant transfected cells (0.93±0.04 1.00±0.02, =1.375, =0.241). Also we found that ectopic expression of miR-138 significantly induced cell cycle arrest at G(1) phase in both suspension and adherent cells (all <0.05). Knockdown of miR-138 had no effect on cell adhesion ability (all >0.05). More importantly, in suspension cells, knockdown of miR-138 significantly decreased the percentage of doxorubicin-induced cell death. However, knockdown of miR-138 dramatically increased the percentage of doxorubicin-induced cell death in FN/HS-5-adherent cells. Furthermore, the miR-138 expression was significantly higher in patients with progression of disease/stable disease than those experiencing complete response/partial response (9.72±1.11 3.06±0.22, =9.144, <0.001). MiR-138 promoted CAM-DR phenotype through cell adhesion-mediated SGTA down-regulation and cell cycle arrest.