MicroRNA-205 downregulates mixed-lineage-AF4 oncogene expression in acute lymphoblastic leukemia.
MicroRNA-205 downregulates mixed-lineage-AF4 oncogene expression in acute lymphoblastic leukemia.
复制标题
MicroRNA-205下调急性淋巴细胞白血病中混合谱系AF4癌基因的表达
DOI：
10.2147/ott.s45376
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发表时间：
2013
影响因子：
4
通讯作者：
Yu L
中科院分区：
文献类型：
--
作者：
Dou L;Li J;Zheng D;Li Y;Gao X;Xu C;Gao L;Wang L;Yu L
髓系/淋巴或混合系AF4急性淋巴细胞白血病（MLL-AF4 ALL）是一种儿童白血病，很少发生在成人中。MLL-AF 4 ALL的典型特征是存在染色体易位（t（4; 11）（q21; q23）），导致MLL-AF 4融合蛋白表达。虽然MLL-AF4融合蛋白触发白血病特有的分子发病机制和血液学表现，但该癌基因在白血病发生中的确切作用仍不清楚。已有研究表明microRNAs（miRs）可能调控MLL-AF 4 ALL融合蛋白的表达，提示miRs参与了MLL-AF 4 ALL的进展或抑制。我们之前已经证明了miR-205负调控MLL-AF4荧光素酶报告基因的转录。在此，我们报道了miR-205在MLL-AF 4人细胞系（RS4; 11和MV4 - 11）中的外源性表达在信使RNA（mRNA）和蛋白质水平上反向调节MLL-AF 4的表达。此外，miR-205显著诱导MLL-AF4细胞的凋亡，如使用荧光激活细胞分选（FACS）分析的Annex in V染色所证明的。白血病细胞的增殖能力被miR-205抑制。添加miR-205抑制剂能够恢复观察到的效果。总之，这些发现表明miR-205可能具有作为治疗MLL-AF 4 ALL的新型治疗剂的潜在价值。
Myeloid/lymphoid or mixed-lineage AF4 acute lymphoblastic leukemia (MLL-AF4 ALL) is a pediatric leukemia that occurs rarely in adults. MLL-AF4 ALL is typically characterized by the presence of chromosomal translocation (t(4;1l)(q21;q23)), leading to expression of MLL-AF4 fusion protein. Although MLL-AF4 fusion protein triggers a molecular pathogenesis and hematological presentations that are unique to leukemias, the precise role of this oncogene in leukemogenesis remains unclear. Previous studies have indicated that microRNAs (miRs) might modulate the expression of MLL-AF4 ALL fusion protein, thereby suggesting the involvement of miR in progression or suppression of MLL-AF4 ALL. We have previously demonstrated that miR-205 negatively regulates transcription of an MLL-AF4 luciferase reporter. Here, we report that exogenous expression of miR-205 in MLL-AF4 human cell lines (RS4;11 and MV4-11) inversely regulates the expression of MLL-AF4 at both messenger RNA (mRNA) and protein level. Furthermore, miR-205 significantly induced apoptosis in MLL-AF4 cells as evidenced by Annex in V staining using fluorescence-activated cell sorting (FACS) analysis. The proliferative capacity of leukemic cells was suppressed by miR-205. The addition of an miR-205 inhibitor was able to restore the observed effects. In conclusion, these findings demonstrate that miR-205 may have potential value as a novel therapeutic agent in the treatment of MLL-AF4 ALL.