Effects of microRNA-20a on the proliferation, migration and apoptosis of multiple myeloma via the PTEN/PI3K/AKT signaling pathway
Effects of microRNA-20a on the proliferation, migration and apoptosis of multiple myeloma via the PTEN/PI3K/AKT signaling pathway
复制标题
microRNA-20a通过PTEN/PI3K/AKT信号通路对多发性骨髓瘤增殖、迁移和凋亡的影响
DOI：
10.3892/ol.2018.8555
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发表时间：
2018-06-01
期刊：
影响因子：
2.9
通讯作者：
Chen, Guoan
中科院分区：
文献类型：
--
作者：
Jiang, Yanxia;Chang, Hong;Chen, Guoan
多发性骨髓瘤（MM）是一种异质性疾病，预后差。循环microRNA（miRNAs）已显示出作为异质性疾病的非侵入性预后生物标志物的潜力。miR-20 a参与多种人类肿瘤的发生发展，其磷酸酶和张力蛋白同源物/磷酸肌醇3-激酶/蛋白激酶B（PTEN/P13 K/Akt）信号通路在细胞增殖、迁移和凋亡中起关键作用。在此，我们研究了miR-20 a在MM细胞增殖、迁移和凋亡过程中对PTEN/PI 3 K/Akt信号通路的影响。应用逆转录定量聚合酶链反应（RT-PCR）检测30例MM患者血浆及MM细胞株中miR-20 a的表达。采用CCK-8法、Transwell法、Annexin V/PI双染法和Western blotting法检测细胞增殖、迁移、周期和凋亡过程中PTEN、PI 3 K和Akt蛋白的表达。在MM细胞中观察到miR-20 a的显著上调和PTEN的失调。我们还鉴定了PTEN作为miR-20 a的下游靶基因，其结合于PTEN的3 '非翻译区。miR-20 a过表达与PTEN蛋白表达降低相关，与空白组和阴性对照组相比，miR-20 a抑制剂处理降低了细胞增殖、迁移和克隆形成，降低了PI 3 K和p-Akt蛋白表达，但增加了PTEN蛋白表达。综上所述，这些结果表明，抑制miR-20 a通过调节PTEN/PI 3 K/Akt信号通路抑制MM进展。这些结果表明，miR-20 a可能是治疗MM的一个新的分子治疗靶点。
Multiple myeloma (MM) is a heterogeneous disease with a poor prognosis. Circulating microRNAs (miRNAs) have shown potential as non-invasive prognostic biomarkers for heterogeneous diseases. miR-20a has been shown involved in various human cancers, and the phosphatase and tensin homolog/phosphoinositide 3-kinase/protein kinase B (PTEN/P13K/Akt) signaling pathway plays a key role in cell proliferation, migration and apoptosis. Here, we investigated the effect of miR-20a on the PTEN/PI3K/Akt signaling pathway during MM cell proliferation, migration and apoptosis. Reverse transcription quantitative polymerase chain reaction was applied to detect miR-20a expression in plasma from 30 MM patients and MM cell lines. CCK-8 assays, Transwell assays, Annexin V/PI double-staining and western blotting were performed to examine the protein expressions of PTEN, PI3K and Akt during cellullar proliferation, migration, cycling, and apoptosis. Significant upregulation of miR-20a and deregulation of PTEN were observed in MM cells. We also identified PTEN as a downstream target gene of miR-20a, which bound to the 3'-untranslated region of PTEN. Overexpression of miR-20a was associated with decreased PTEN expression, and treatment with miR-20a inhibitors decreased cell proliferation, migration and clonogenicity and reduced the protein expressions of PI3K and p-Akt but increased PTEN protein expression compared with blank and negative control groups. Taken together, these results showed that inhibition of miR-20a suppresses MM progression by modulating the PTEN/PI3K/Akt signaling pathway. These findings suggest that miR-20a may be a novel molecular therapeutic target for the treatment of MM.