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MicroRNA-532 exerts oncogenic functions in t(4;14) multiple myeloma by targeting CAMK2N1

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Abstract

Multiple myeloma (MM) is a plasma cell neoplasm which is characterized by widespread genetic heterogeneity. The MMs with t(4;14) translocation exhibit poor outcomes. However, the mechanism underlying has not been well dissected. Our study aimed to identify key microRNA involved in the oncogenesis of t(4;14) MM. We here performed an integrated analysis to screen important regulators in the pathogenesis of t(4;14) MM. We used real-time quantitative polymerase chain reaction and western blotting to evaluate the mRNA and protein expression of the indicated microRNA or protein. Cell proliferation assay, colony formation assay, and transwell assay were used to examine the cell growth and metastasis. More importantly, the tumor growth and metastasis were analyzed in nude mice injected with MM cells. The integrated analysis indicated that miR-532 functioned as a pivotal regulator in t(4;14) MM. miR-532 was upregulated in t(4;14) MMs and promotes cell growth and metastasis in vitro and in vivo. Notably, though combing bioinformatics analysis and functional assays, CAMK2N1 was revealed as a functional target of miR-532 in MM cells. CAMK2N1 plays an anti-proliferative and anti-migration role in MM cells, and miR-532 exerts its oncogenic role though inhibiting CAMK2N1 expression in MMs. miR-532 promotes cell proliferation and invasion in t(4;14) MMs by targeting CAMK2N1. Our study, thus, provides possible targets for t(4;14) MM therapy.

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Acknowledgements

This work was supported by Natural Science Foundation of Ningbo Municipality (Grant No. 2017A610210).

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Authors and Affiliations

  1. Department of Hematology, Ningbo First Hospital, No. 59 Liuting Street, Ningbo, Zhejiang, 315000, China

    Kaihong Xu, Guifang Ouyang, Yanli Zhang, Qitian Mu & Xiao Yan

  2. Department of Emergency Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China

    Xuezhen Hu & Laifang Sun

  3. Department of Nutrition, The Second Clinical Medical College of Chengdu University of Traditional Chinese Medicine, Guangan, Sichuan, 638500, China

    Qingyue Liang

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  1. Kaihong Xu
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Correspondence to Kaihong Xu.

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All animal experiments were conducted in accordance with the guidelines of the Ningbo First Hospital Animal Care and Use Committee. All procedures performed in studies involving human participants were approved by the ethics committee of the Ningbo First Hospital.

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Xu, K., Hu, X., Sun, L. et al. MicroRNA-532 exerts oncogenic functions in t(4;14) multiple myeloma by targeting CAMK2N1. Human Cell 32, 529–539 (2019). https://doi.org/10.1007/s13577-019-00276-y

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