miR-29b suppresses CML cell proliferation and induces apoptosis via regulation of BCR/ABL1 protein
miR-29b suppresses CML cell proliferation and induces apoptosis via regulation of BCR/ABL1 protein
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DOI：
10.1016/j.yexcr.2013.02.002
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发表时间：
2013-05-01
影响因子：
3.7
通讯作者：
Feng, Wenli
中科院分区：
文献类型：
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作者：
Li, Yajuan;Wang, Haixia;Feng, Wenli
microRNAs（miRNAs）是一类转录后调节基因表达的小分子RNA，在许多细胞通路中起重要作用。最近的证据表明，异常的miRNA表达谱和独特的miRNA信号通路存在于许多癌症中。在这里，我们证明了miR-29 b在CML患者样本中的表达显著降低。生物信息学分析揭示了miR-29 b在ABL 1的3 '-非翻译区（UTR）中的保守靶位点。miR-29 b显著抑制含有ABL 1 - 3 'UTR的荧光素酶报告基因的活性，并且在用突变的ABL 1 - 3' UTR转染的细胞中未观察到该活性。miR-29 b在K562细胞中的增强表达抑制细胞生长和集落形成能力，从而通过切割半胱氨酸蛋白酶原3和PARP诱导细胞凋亡。此外，用靶向ABL 1的siRNA转染的K562细胞显示出与miR-29 b过表达的细胞相似的生长和凋亡表型。总之，我们的研究结果表明，miR-29 b可能通过靶向ABL 1和BCR/ABL 1发挥肿瘤抑制作用。(c)2013 Elsevier Inc. All rights reserved.
MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally and are critical for many cellular pathways. Recent evidence has shown that aberrant miRNA expression profiles and unique miRNA signaling pathways are present in many cancers. Here, we demonstrate that miR-29b is markedly lower expressed in CML patient samples. Bioinformatics analysis reveals a conserved target site for miR-29b in the 3'-untranslated region (UTR) of ABL1. miR-29b significantly suppresses the activity of a luciferase reporter containing ABL1-3'UTR and this activity is not observed in cells transfected with mutated ABL1-3'UTR. Enforced expression of miR-29b in K562 cells inhibits cell growth and colony formation ability thereby inducing apoptosis through cleavage of procaspase 3 and PARP. Furthermore, K562 cells transfected with a siRNA targeting ABL1 show similar growth and apoptosis phenotypes as cells overexpression of miR-29b. Collectively, our results suggest that miR-29b may function as a tumor suppressor by targeting ABL1 and BCR/ABL1. (c) 2013 Elsevier Inc. All rights reserved.