miR-202 contributes to sensitizing MM cells to drug significantly via activing JNK/SAPK signaling pathway
10.3760/cma.j.issn.0253-2727.2016.11.012
- VernacularTitle:microRNA-202激活JNK/SAPK信号通路增强多发性骨髓瘤细胞药物敏感性的研究
- Author:
Yan ZHANG
1
;
Xianjuan SHEN
;
Xinhua WU
;
Hui CONG
;
Hongbing NI
;
Shaoqing JU
;
Jianyou SU
Author Information
1. 226001,南通大学附属医院检验医学中心
- Keywords:
Multiple myeloma;
MicroRNAs;
Drug resistance,neoplasm;
Signaling pathway
- From:
Chinese Journal of Hematology
2016;37(11):987-992
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role of miR-202 in multiple myeloma (MM) cells,and study the regulation of miR-202 on drug sensitivity of MM cells.Methods miR-202 and BAFF mRNA levels were detected by real-time PCR.U266 cells were transfected with miR-202-mimics,miR-202-inhibitor,siBAFF and their negative controls.After above treatments,protein levels of Bcl-2 family and MAPK signaling pathway were detected by Western blot analysis,and the proliferation and apoptosis ability of MM cells were examined by WST-1,Annexin Ⅴ-FLUOS assay,respectively.Results The results showed that the expression ofmiR-202 in CD138+ MM cells (0.304±0.354) and U266 cells (0.052± 0.009) were lower than in normal controls (3.550± 1.126) (P＜0.001,P=0.009),whereas BAFF mRNA levels (5.700±0.734,9.576±2.887) were higher than in normal controls (1.819±0.853) (P＜0.001,P=0.006).The proliferation ability of U266 cells transfected with miR-202 mimics was significantly inhibited than in control group [(56.04±0.021)％ vs (18.89±0.32)％,P=0.002].The result of Western blot showed that the expression of Bcl-2 decreased by about 24％,and the expression of Bax increased by about 124％ in cells transfected with miR-202 mimics.The apoptosis rate in cells transfected with miR-202 mimics was significantly more than in control group [(49.60±4.89)％ vs (26.20±1.28)％,P=0.029].The apoptosis rate in miR-202 mimics combined with Bort group (51.23±5.41)％ was higher as compared with Bort treatment alone (31.70±4.40) ％ or miR-202 mimics control combined with Bort group (27.94±4.04) ％,(P=0.047,P=0.028),whereas the apoptosis rate in miR-202 mimics combined with Thal or Dex had no significant difference compared with miR-202 mimics control [(11.66±1.91)％ vs (10.63±1.74)％,P=0.700;(16.35± 1.32)％ vs (17.43 ± 1.95)％,P=0.400].The inhibitory rate of cell growth in miR-202 mimics combined with Bort group was higher as compared with Bort treatment alone [(36.93±5.98)％ vs (18.18±4.10)％,P=0.029].The expressions of p-JNK protein decreased in U266 cells transfected with miR-202 mimics and treated with Bort.Conclusion miR-202 mimics combined with Bort could inhibit proliferation and induce apoptosis of U266 cells through negative regulating target gene BAFF,which further inhibited the JNK/ SAPK signaling pathway.
