MicroRNA-497 inhibits multiple myeloma growth and increases susceptibility to bortezomib by targeting Bcl-2
MicroRNA-497 inhibits multiple myeloma growth and increases susceptibility to bortezomib by targeting Bcl-2
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MicroRNA-497 通过靶向 Bcl-2 抑制多发性骨髓瘤生长并增加对硼替佐米的敏感性
DOI：
10.3892/ijmm.2018.4019
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发表时间：
2019-02-01
影响因子：
5.4
通讯作者：
Jiang, Jian
中科院分区：
文献类型：
--
作者：
Tian, Faqing;Zhan, Yong;Jiang, Jian
多发性骨髓瘤（multiple myeloma，MM）是一种常见于老年人的严重造血系统恶性肿瘤。先前报道microRNA（miR）-497有助于其他细胞类型的凋亡，推测是通过靶向B细胞淋巴瘤2（Bcl-2）。在本研究中，miRNA和蛋白质表达水平分别通过逆转录-定量聚合酶链反应和蛋白质印迹分析。采用3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物和平板克隆形成试验测定细胞增殖和活力，并采用流式细胞仪测定细胞生长周期。采用末端脱氧核苷酸转移酶（TdT）介导的dUTP缺口末端标记法、Annexin V和caspase-3活性测定法检测细胞凋亡率。结果显示，在MM组织和细胞系中，miR-497显著降低，而Bcl-2增强。miR-497靶向Bcl-2并影响其下游凋亡相关基因。miR-497过表达可通过细胞周期阻滞促进MM细胞凋亡，降低集落形成能力和生存力。此外，miR-497增加了MM细胞对硼替佐米的敏感性。总之，miR-497通过直接靶向Bcl-2和改变下游凋亡相关蛋白的表达来抑制MM细胞增殖并促进凋亡。miR-497和硼替佐米的组合可以增强药物敏感性，作为MM的潜在可用治疗方法。
Multiple myeloma (MM) is a common severe hematopoietic malignancy occuring in aged population. MicroRNA (miR)-497 was previously reported to contribute to the apoptosis of other cell types, presumably through targeting B-cell lymphoma 2 (Bcl-2). In the present study, miRNA and protein expression levels were detected by reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. The cell proliferation and viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and plate clonality assays, and the cell growth cycle was measured with a flow cytometer. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling, Annexin V and caspase-3 activity assays were performed to examine the cell apoptotic rates. The results showed that miR-497 was markedly decreased, whereas Bcl-2 was enhanced in MM tissues and cell lines. miR-497 targeted Bcl-2 and affected its downstream apoptosis-related genes. The overexpression of miR-497 promoted MM cell apoptosis through cell cycle arrest, and decreased colony genesis ability and viability. In addition, miR-497 increased the sensitivity of MM cells to bortezomib. Taken together, miR-497 suppressed MM cell proliferation and promoted apoptosis by directly targeting Bcl-2 and altering the expression of downstream apoptosis-related proteins. The combination of miR-497 and bortezomib may enhance drug sensitivity, serving as a potentially available therapeutic method for MM.