Aberrant microRNA-182 expression is associated with glucocorticoid resistance in lymphoblastic malignancies
Aberrant microRNA-182 expression is associated with glucocorticoid resistance in lymphoblastic malignancies
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DOI：
10.3109/10428194.2012.693178
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发表时间：
2012-12-01
影响因子：
2.6
通讯作者：
Xie, Yanhui
中科院分区：
文献类型：
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作者：
Yang, Apeng;Ma, Jiexian;Xie, Yanhui
淋巴细胞恶性肿瘤的糖皮质激素（GC）耐药性与治疗失败有关，是预后不良的标志。先前的研究表明，microRNA-182 （miR-182）作为一种致癌基因，通过调控FOXO3A在肿瘤发生中发挥作用。FOXO3A与肿瘤抑制和gc诱导的细胞凋亡有关，这表明FOXO3A具有作为治疗靶点的潜力。在此，我们研究了miR-182在淋巴细胞恶性肿瘤中GC敏感性中的作用。miR-182在人和小鼠气相色谱耐药细胞系中的表达始终高于气相色谱敏感细胞系。此外，miR-182表达的增加降低了FOXO3A的总表达，但对phospho-FOXO3A没有显著影响。此外，作为FOXO3A的下游靶点，Bim通过过表达miR-182而减少，通过下调miR-182而增加。这些结果表明，miR-182通过靶向FOXO3A参与糖皮质激素耐药，并且恢复miR-182是淋巴细胞恶性肿瘤潜在的有前途的治疗策略。
Glucocorticoid (GC) resistance in lymphoblastic malignancies is related to treatment failure and is a marker of poor prognosis. Previous studies have suggested that microRNA-182 (miR-182) functions as an oncogene and plays a role in tumorigenesis, through regulation of FOXO3A. FOXO3A has been implicated in tumor suppression and GC-induced apoptosis, suggesting that FOXO3A has potential as a therapeutic target. Herein we investigated the role of miR-182 in GC sensitivity in lymphoblastic malignancies. Expression of miR-182 was consistently higher in human and mouse GC-resistant cell lines than in GC-sensitive cell lines. Furthermore, increased expression of miR-182 reduced total FOXO3A expression but had no significant effect on phospho-FOXO3A. Additionally Bim, as a downstream target of FOXO3A, was reduced by overexpression of miR-182, and increased by down-regulation of miR-182. These results demonstrate that miR-182 is involved in glucocorticoid resistance, via targeting of FOXO3A, and that restoration of miR-182 is a potentially promising therapeutic strategy in lymphoblastic malignancies.