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Integrative analysis of signaling pathways and diseases associated with the miR-106b/25 cluster and their function study in berberine-induced multiple myeloma cells

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Abstract

Berberine (BBR), a traditional Chinese herbal medicine compound, has emerged as a novel class of anti-tumor agent. Our previous microRNA (miRNA) microarray demonstrated that miR-106b/25 was significantly down-regulated in BBR-treated multiple myeloma (MM) cells. Here, systematic integration showed that miR-106b/25 cluster is involved in multiple cancer-related signaling pathways and tumorigenesis. MiREnvironment database revealed that multiple environmental factors (drug, ionizing radiation, hypoxia) affected the miR-106b/25 cluster expression. By targeting the seed region in the miRNA, tiny anti-mir106b/25 cluster (t-anti-mir106b/25 cluster) significantly induced suppression in cell viability and colony formation. Western blot validated that t-anti-miR-106b/25 cluster effectively inhibited the expression of P38 MAPK and phospho-P38 MAPK in MM cells. These findings indicated the miR-106b/25 cluster functioned as oncogene and might provide a novel molecular insight into MM.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (no. 81170496), Research Project for Practice Development of National TCM Clinical Research Bases (no. JDZX2015119), and Science and Technology Program of Guangdong Province (no. 2012B031800474, 2013B021800151, 2014A020212729).

Authors’ contributions

JF conceived and designed the experiments. CG, TL, and ZY performed the experiments. JF and SC analyzed the data. JS and JF contributed reagents, materials, and analytical tools. JF and YZ wrote the paper.

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    Authors and Affiliations

    1. Department of Biochemistry and Molecular Biology, Medical College of Jinan University, 601 Western Huangpu Avenue, 510632, Guangzhou, China

      Chunming Gu, Zhao Yin & Jia Fei

    2. Institute of Chinese Integrative Medicine, Medical College of Jinan University, Guangzhou, 510632, China

      Chunming Gu & Jia Fei

    3. Department of Clinical Medicine, Medical College of Jinan University, Guangzhou, 510632, China

      Tianfu Li

    4. Department of Blood Transfusion, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China

      Shengting Chen

    5. Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China

      Jianping Shen

    6. Institute of Hematology, Medical College of Jinan University, Guangzhou, 510632, China

      Yuan Zhang

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    1. Chunming Gu
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    Correspondence to Jia Fei or Jianping Shen.

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    This article forms part of a special issue of Functional and Integrative Genomics entitled “miRNA in model and complex organisms” (Issue Editors: Hikmet Budak and Baohong Zhang)

    Chunming Gu, Tianfu Li and Zhao Yin contributed equally to this work.

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    Gu, C., Li, T., Yin, Z. et al. Integrative analysis of signaling pathways and diseases associated with the miR-106b/25 cluster and their function study in berberine-induced multiple myeloma cells. Funct Integr Genomics 17, 253–262 (2017). https://doi.org/10.1007/s10142-016-0519-7

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