MicroRNA-138 regulates cell adhesion-mediated drug resistance phenotype by targeting SGTA in non-Hodgkin's lymphoma.
10.3760/cma.j.issn.0253-2727.2018.08.011
- Author:
Ya Xun WU
;
Song HE
;
Xiao Hong XU
1
Author Information
1. Department of Oncology, Nantong Cancer Hospital, Nantong 226361, China.
- Publication Type:Journal Article
- Keywords:
Cell adhesion-mediated drug resistance;
Micro RNAs;
Non-Hodgkin's lymphoma;
SGTA
- MeSH:
Carrier Proteins;
Cell Adhesion;
Cell Line, Tumor;
Cell Proliferation;
Drug Resistance, Neoplasm;
Gene Expression Regulation, Neoplastic;
Humans;
Lymphoma, Non-Hodgkin;
MicroRNAs;
Molecular Chaperones;
Phenotype
- From:
Chinese Journal of Hematology
2018;39(8):668-673
- CountryChina
- Language:Chinese
-
Abstract:
Objective: 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). Methods: 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. Results: Our data showed that adhesion of NHL cells to FN or HS-5 cells significantly increased miR-138 expression (P<0.05). Knockdown of miR-138 markedly increased the protein (all P<0.05) but not for mRNA (all P>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 vs 1.00±0.02, t=0.914, P=0.002). No change in terms of reporter activity was observed in SGTA 3'UTR mutant transfected cells (0.93±0.04 vs 1.00±0.02, t=1.375, P=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 P<0.05). Knockdown of miR-138 had no effect on cell adhesion ability (all P>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 vs 3.06±0.22, t=9.144, P<0.001). Conclusion: MiR-138 promoted CAM-DR phenotype through cell adhesion-mediated SGTA down-regulation and cell cycle arrest.
