Study on the Association Between miRNA-202 Expression and Drug Sensitivity in Multiple Myeloma Cells
Study on the Association Between miRNA-202 Expression and Drug Sensitivity in Multiple Myeloma Cells
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DOI：
10.1007/s12253-015-0035-4
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发表时间：
2016-07-01
影响因子：
2.8
通讯作者：
Ju, Shaoqing
中科院分区：
文献类型：
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作者：
Shen, Xianjuan;Guo, Yuehua;Ju, Shaoqing
越来越多的实验证据表明 miRNA 在血液肿瘤发生中发挥因果作用。在这项研究中，我们表征了 miR-202 在多发性骨髓瘤 (MM) 药物敏感性中的作用。通过荧光素酶报告基因测定证实了 miR-202 和 B 细胞激活因子 (BAFF) 的潜在结合位点。 MM细胞用miR-202模拟物和抑制剂转染。通过WST-1细胞增殖测定和Annexin V-FLUOS细胞凋亡测定来测量细胞生长。通过实时 PCR 测量 BAFF 和 miR-202 mRNA 水平。同时通过Western blot检测BAFF、Bcl-2家族存活蛋白和MAPK通路蛋白。研究发现miR-202作为BAFF表达的调节剂发挥作用。 miR-202 过表达使 MM 细胞对硼替佐米 (Bort) 敏感，但对沙利度胺 (Thal) 和地塞米松 (Dex) 敏感。与单独使用 Bort 治疗相比，miR-202 模拟物与 Bort 联合使用更有效地抑制 MM 细胞存活。我们的研究还提供了实验证据表明JNK/SAPK信号通路参与了miR-202对MM细胞耐药性的调节作用。这些结果表明 miR-202 表达的调节机制可能是微调抗骨髓瘤治疗的有希望的靶点。
An increasing amount of experimental evidence has shown that miRNAs play a causal role in hematologic tumorigenesis. In this study, we characterized the role of miR-202 in multiple myeloma (MM) drug sensitivity. The potential binding site of miR-202 and B cell-activating factor (BAFF) was confirmed by luciferase reporter assay. MM cells were transfected with miR-202 mimics and inhibitor. Cells growth was measured by WST-1 cell proliferation assay and Annexin V-FLUOS apoptosis assay. BAFF and miR-202 mRNA levels were measured by real-time PCR. Meanwhile, BAFF, Bcl-2 family survival proteins and MAPK pathway proteins were measured by Western blot. It was found that miR-202 was functioned as a modulator of BAFF expression. miR-202 over-expression sensitized MM cells to bortezomib (Bort) but less to Thalidomide (Thal) and dexamethasone (Dex). miR-202 mimics in combination with Bort inhibited MM cell survival more effectively as compared with Bort treatment alone. Our study also provided experimental evidence that JNK/SAPK signaling pathway was involved in the regulatory effect of miR-202 on drug resistance of MM cells. These results suggest that the regulatory mechanism of miR-202 expression may be a promising target for fine-tuning anti-myeloma therapy.