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Study on the Association Between miRNA-202 Expression and Drug Sensitivity in Multiple Myeloma Cells

  • Original Article
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Pathology & Oncology Research

Abstract

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.

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Acknowledgments

XJS and YHG carried out the cell proliferation assay, participated in the cell culture and drafted the manuscript. JQ carried out the immunoassays. WS and XHW participated in the cell survival and growth and PCR assay. HBN carried out apoptosis assay. SQJ conceived of the study, participated in its design and coordination, analysis the data and revised the manuscript.

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Authors and Affiliations

  1. Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, #20 Xisi Road, Nantong, 226001, JS, People’s Republic of China

    Xianjuan Shen, Jing Qi, Wei Shi, Xinhua Wu & Shaoqing Ju

  2. Nantong University, #9 Seyuan Road, Nantong, 226001, JS, People’s Republic of China

    Yuehua Guo & Shaoqing Ju

  3. Laboratory Medicine Center, Affiliated Hospital of Nantong University, #20 Xisi Road, Nantong, 226001, JS, People’s Republic of China

    Hongbing Ni & Shaoqing Ju

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  1. Xianjuan Shen
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  2. Yuehua Guo
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  3. Jing Qi
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  4. Wei Shi
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Correspondence to Shaoqing Ju.

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Grand Support

The National Nature Science Foundation of China (81,301,498; 81,271,920; 81,201,351); Jiangsu Provincial Medical Innovation Team and Leading Talents (LJ201133); the Scientific Research Subject of Jiangsu Provincial Health Department (H201422); and the Six Major Human Resource Projects of Jiangsu Province (20,012-WS-119)

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Shen, X., Guo, Y., Qi, J. et al. Study on the Association Between miRNA-202 Expression and Drug Sensitivity in Multiple Myeloma Cells. Pathol. Oncol. Res. 22, 531–539 (2016). https://doi.org/10.1007/s12253-015-0035-4

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  • DOI: https://doi.org/10.1007/s12253-015-0035-4

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