Department of Hematology, Ningbo First Hospital, No. 59 Liuting Street, Ningbo, Zhejiang, 315000, China.
Department of Emergency Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Hum Cell. 2019 Oct;32(4):529-539. doi: 10.1007/s13577-019-00276-y. Epub 2019 Aug 26.
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.
多发性骨髓瘤（MM）是一种浆细胞瘤，其特征是广泛的遗传异质性。具有 t(4;14)易位的 MMs 预后不良。然而，其潜在机制尚未得到很好的剖析。我们的研究旨在鉴定与 t(4;14) MM 发生相关的关键 microRNA。我们在此进行了综合分析，以筛选 t(4;14) MM 发病机制中的重要调节因子。我们使用实时定量聚合酶链反应和蛋白质印迹法来评估所指示的 microRNA 或蛋白质的 mRNA 和蛋白表达。细胞增殖测定、集落形成测定和 Transwell 测定用于检测细胞生长和转移。更重要的是，在注射 MM 细胞的裸鼠中分析了肿瘤生长和转移。综合分析表明，miR-532 是 t(4;14) MM 的关键调节因子。miR-532 在 t(4;14) MMs 中上调，并促进体外和体内的细胞生长和转移。值得注意的是，尽管结合了生物信息学分析和功能测定，CAMK2N1 被揭示为 MM 细胞中 miR-532 的功能靶标。CAMK2N1 在 MM 细胞中发挥抗增殖和抗迁移作用，而 miR-532 通过抑制 MMs 中 CAMK2N1 的表达发挥其致癌作用。miR-532 通过靶向 CAMK2N1 促进 t(4;14) MMs 中的细胞增殖和侵袭。因此，我们的研究为 t(4;14) MM 的治疗提供了可能的靶点。
